rna interference

Summary

Summary: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX (RISC). DNA METHYLATION may also be triggered during this process.

Top Publications

  1. doi Identification of host proteins required for HIV infection through a functional genomic screen
    Abraham L Brass
    Department of Genetics, Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 319:921-6. 2008
  2. doi Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
    Witold Filipowicz
    Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
    Nat Rev Genet 9:102-14. 2008
  3. pmc Small silencing RNAs: an expanding universe
    Megha Ghildiyal
    Department of Biochemistry and Molecular Pharmacology and Howard Hughes Medical Institute, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
    Nat Rev Genet 10:94-108. 2009
  4. ncbi Prediction of mammalian microRNA targets
    Benjamin P Lewis
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 115:787-98. 2003
  5. pmc Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication
    Renate König
    Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 135:49-60. 2008
  6. pmc Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs
    Rui Yi
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Genes Dev 17:3011-6. 2003
  7. ncbi Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
    D D Sarbassov
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 307:1098-101. 2005
  8. doi Genome-scale RNAi screen for host factors required for HIV replication
    Honglin Zhou
    Department of Virus and Cell Biology, Merck and Co, Inc, West Point, PA 19486, USA
    Cell Host Microbe 4:495-504. 2008
  9. pmc Intronic microRNA precursors that bypass Drosha processing
    J Graham Ruby
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 448:83-6. 2007
  10. pmc Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs
    John L Rinn
    Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 129:1311-23. 2007

Detail Information

Publications386 found, 100 shown here

  1. doi Identification of host proteins required for HIV infection through a functional genomic screen
    Abraham L Brass
    Department of Genetics, Center for Genetics and Genomics, Brigham and Women s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 319:921-6. 2008
    ..This effort illustrates the power with which RNA interference and forward genetics can be used to expose the dependencies of human pathogens such as HIV, and in so doing ..
  2. doi Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
    Witold Filipowicz
    Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland
    Nat Rev Genet 9:102-14. 2008
    ..This Review summarizes the current understanding of the mechanistic aspects of microRNA-induced repression of translation and discusses some of the controversies regarding different modes of microRNA function...
  3. pmc Small silencing RNAs: an expanding universe
    Megha Ghildiyal
    Department of Biochemistry and Molecular Pharmacology and Howard Hughes Medical Institute, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
    Nat Rev Genet 10:94-108. 2009
    ....
  4. ncbi Prediction of mammalian microRNA targets
    Benjamin P Lewis
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 115:787-98. 2003
    ..The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions...
  5. pmc Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication
    Renate König
    Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 135:49-60. 2008
    ..Taken together, the multiscale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate the early steps of HIV-1 infection...
  6. pmc Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs
    Rui Yi
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Genes Dev 17:3011-6. 2003
    ..Together, these findings define an additional cellular cofactor required for miRNA biogenesis and function...
  7. ncbi Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
    D D Sarbassov
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Science 307:1098-101. 2005
    ..Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation...
  8. doi Genome-scale RNAi screen for host factors required for HIV replication
    Honglin Zhou
    Department of Virus and Cell Biology, Merck and Co, Inc, West Point, PA 19486, USA
    Cell Host Microbe 4:495-504. 2008
    ..This study highlights both the power and shortcomings of large scale loss-of-function screens in discovering host-pathogen interactions...
  9. pmc Intronic microRNA precursors that bypass Drosha processing
    J Graham Ruby
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 448:83-6. 2007
    ..This suggests that other lineages with many similarly sized introns probably also have mirtrons, and that the mirtron pathway could have provided an early avenue for the emergence of miRNAs before the advent of Drosha...
  10. pmc Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs
    John L Rinn
    Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Cell 129:1311-23. 2007
    ..Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states...
  11. ncbi Human RISC couples microRNA biogenesis and posttranscriptional gene silencing
    Richard I Gregory
    The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    Cell 123:631-40. 2005
    b>RNA interference is implemented through the action of the RNA-induced silencing complex (RISC)...
  12. pmc Human host factors required for influenza virus replication
    Renate König
    Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research
    Nature 463:813-7. 2010
    ..Here we use an integrative systems approach, based on genome-wide RNA interference screening, to identify 295 cellular cofactors required for early-stage influenza virus replication...
  13. ncbi Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes
    Christian Matranga
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Cell 123:607-20. 2005
    In the Drosophila and mammalian RNA interference pathways, siRNAs direct the protein Argonaute2 (Ago2) to cleave corresponding mRNA targets, silencing their expression. Ago2 is the catalytic component of the RNAi enzyme complex, RISC...
  14. pmc MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells
    Margaret S Ebert
    Center for Cancer Research, E17 529B Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nat Methods 4:721-6. 2007
    ..RNA polymerase II promoter (Pol II)-driven sponges contain a fluorescence reporter gene for identification and sorting of sponge-treated cells. We envision the use of stably expressed sponges in animal models of disease and development...
  15. pmc Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes
    Beate Neumann
    MitoCheck Project Group, European Molecular Biology Laboratory EMBL, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Nature 464:721-7. 2010
    ..fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing...
  16. ncbi Argonaute proteins: key players in RNA silencing
    Gyorgy Hutvagner
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK
    Nat Rev Mol Cell Biol 9:22-32. 2008
    ..With their functional domains, Argonaute proteins can bind small non-coding RNAs and control protein synthesis, affect messenger RNA stability and even participate in the production of a new class of small RNAs, Piwi-interacting RNAs...
  17. doi Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication
    Alexander Karlas
    Molecular Biology Department, Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany
    Nature 463:818-22. 2010
    ..report the discovery of 287 human host cell genes influencing influenza A virus replication in a genome-wide RNA interference (RNAi) screen...
  18. ncbi The nuclear RNase III Drosha initiates microRNA processing
    Yoontae Lee
    Institute of Molecular Biology and Genetics and School of Biological Sciences, Seoul National University, Seoul 151 742, Korea
    Nature 425:415-9. 2003
    ..Immunopurified Drosha cleaved pri-miRNA to release pre-miRNA in vitro. Furthermore, RNA interference of Drosha resulted in the strong accumulation of pri-miRNA and the reduction of pre-miRNA and mature miRNA in ..
  19. doi A human snoRNA with microRNA-like functions
    Christine Ender
    Center for Integrated Protein Science Munich CIPSM, Laboratory of RNA Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Mol Cell 32:519-28. 2008
    ..We further identify a number of human snoRNAs with microRNA (miRNA)-like processing signatures. We have, therefore, identified a class of small RNAs in human cells that originate from snoRNAs and can function like miRNAs...
  20. doi Knocking down barriers: advances in siRNA delivery
    Kathryn A Whitehead
    Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Nat Rev Drug Discov 8:129-38. 2009
    In the 10 years that have passed since the Nobel prize-winning discovery of RNA interference (RNAi), billions of dollars have been invested in the therapeutic application of gene silencing in humans...
  21. pmc MicroRNA genes are transcribed by RNA polymerase II
    Yoontae Lee
    Institute of Molecular Biology and Genetics and School of Biological Science, Seoul National University, Seoul, Korea
    EMBO J 23:4051-60. 2004
    ..These data indicate that pol II is the main, if not the only, RNA polymerase for miRNA gene transcription. Our study offers a basis for understanding the structure and regulation of miRNA genes...
  22. pmc RNA interference screen for human genes associated with West Nile virus infection
    Manoj N Krishnan
    Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticutt 06520 8031, USA
    Nature 455:242-5. 2008
    ..b>RNA interference (RNAi) presents a powerful forward genetics approach to dissect virus-host cell interactions...
  23. doi PIWI-interacting small RNAs: the vanguard of genome defence
    Mikiko C Siomi
    Keio University School of Medicine, Tokyo 160 8582, Japan
    Nat Rev Mol Cell Biol 12:246-58. 2011
    ..Now, much progress is being made into our understanding of their biogenesis and molecular functions, including the specific subcellular compartmentalization of the piRNA pathway in granular cytoplasmic bodies...
  24. pmc Origins and Mechanisms of miRNAs and siRNAs
    Richard W Carthew
    Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208 3500, USA
    Cell 136:642-55. 2009
    ..Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment...
  25. ncbi Opposing activities protect against age-onset proteotoxicity
    Ehud Cohen
    Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 313:1604-10. 2006
    ..Because the IIS pathway is central to the regulation of longevity and youthfulness in worms, flies, and mammals, these results suggest a mechanistic link between the aging process and aggregation-mediated proteotoxicity...
  26. ncbi Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton
    D D Sarbassov
    Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Curr Biol 14:1296-302. 2004
    ..We find that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals...
  27. pmc High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome
    Sam Alsford
    London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom
    Genome Res 21:915-24. 2011
    ..We describe a high-throughput phenotyping approach termed RNA interference (RNAi) target sequencing, or RIT-seq that, using Illumina sequencing, maps fitness-costs associated with RNAi...
  28. pmc Cleavage of the siRNA passenger strand during RISC assembly in human cells
    Philipp J F Leuschner
    Institute of Molecular Biotechnology of the Austrian Academy of Sciences, IMBA, Dr Bohr Gasse 3 5, 1030 Vienna, Austria
    EMBO Rep 7:314-20. 2006
    A crucial step in the RNA interference (RNAi) pathway involves the assembly of RISC, the RNA-induced silencing complex...
  29. ncbi Systematic functional analysis of the Caenorhabditis elegans genome using RNAi
    Ravi S Kamath
    Wellcome Trust Cancer Research UK Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
    Nature 421:231-7. 2003
    ..Here we describe the use of RNA interference to inhibit the function of approximately 86% of the 19,427 predicted genes of C. elegans...
  30. pmc The Drosha-DGCR8 complex in primary microRNA processing
    Jinju Han
    School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, 151 742, Korea
    Genes Dev 18:3016-27. 2004
    ..Based on these results, we propose a model for the action mechanism of class II RNase III proteins...
  31. ncbi Illuminating the silence: understanding the structure and function of small RNAs
    Tariq M Rana
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Nat Rev Mol Cell Biol 8:23-36. 2007
    b>RNA interference (RNAi) is triggered by double-stranded RNA helices that have been introduced exogenously into cells as small interfering (si)RNAs or that have been produced endogenously from small non-coding RNAs known as microRNAs (..
  32. ncbi UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development
    Karl Agger
    Biotech Research and Innovation Centre BRIC, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen, Denmark
    Nature 449:731-4. 2007
    ..8) supports a model in which the coordinated removal of repressive marks, polycomb group displacement, and deposition of activating marks are important for the stringent regulation of transcription during cellular differentiation...
  33. pmc Chromatin-associated RNA interference components contribute to transcriptional regulation in Drosophila
    Filippo M Cernilogar
    Dulbecco Telethon Institute, Epigenetics and Genome Reprogramming, IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano 64, 00143 Rome, Italy
    Nature 480:391-5. 2011
    b>RNA interference (RNAi) pathways have evolved as important modulators of gene expression that operate in the cytoplasm by degrading RNA target molecules through the activity of short (21-30 nucleotide) RNAs...
  34. pmc OrthoList: a compendium of C. elegans genes with human orthologs
    Daniel D Shaye
    Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America
    PLoS ONE 6:e20085. 2011
    ..We sought to assess the orthology between C. elegans and human genes to understand better the relationship between their genomes and to generate a compelling list of candidates to streamline RNAi-based screens in this model...
  35. pmc Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex
    Yanli Wang
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 456:921-6. 2008
    ..Consistent with the geometry of the ternary complex, bulges residing in the seed segments of the target, but not the guide strand, were better accommodated and their complexes were catalytically active...
  36. doi Small silencing RNAs in plants are mobile and direct epigenetic modification in recipient cells
    Attila Molnar
    Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, UK
    Science 328:872-5. 2010
    ..Mobile sRNA thus represents a mechanism for transmitting the specification of epigenetic modification and could affect genome defense and responses to external stimuli that have persistent effects in plants...
  37. pmc RNA interference in the nucleus: roles for small RNAs in transcription, epigenetics and beyond
    Stephane E Castel
    Watson School of Biological Sciences, Cold Spring Harbor Laboratory, New York 11724, USA
    Nat Rev Genet 14:100-12. 2013
    A growing number of functions are emerging for RNA interference (RNAi) in the nucleus, in addition to well-characterized roles in post-transcriptional gene silencing in the cytoplasm...
  38. pmc RNAi-mediated targeting of heterochromatin by the RITS complex
    Andre Verdel
    Department of Cell Biology, Harvard Medical School, Boston, MA02115, USA
    Science 303:672-6. 2004
    b>RNA interference (RNAi) is a widespread silencing mechanism that acts at both the posttranscriptional and transcriptional levels...
  39. ncbi Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis
    Subham Basu
    Signal Transduction, Cancer Research UK London Research Institue, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Mol Cell 11:11-23. 2003
    ..Akt phosphorylation of YAP may thus suppress the induction of the proapoptotic gene expression response following cellular damage...
  40. ncbi CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry
    M Vig
    Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Science 312:1220-3. 2006
    ..We performed a genome-wide RNA interference (RNAi) screen in Drosophila cells to identify proteins that inhibit store-operated Ca2+ influx...
  41. ncbi A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer
    Katrien Berns
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cancer Cell 12:395-402. 2007
    A large-scale RNA interference screen to discover genes involved in trastuzumab resistance in breast cancer identified only PTEN as a modulator of drug sensitivity...
  42. pmc Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes
    Oliver H Tam
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences and Howard Hughes Medical Institute, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nature 453:534-8. 2008
    ..Our findings indicate a function for pseudogenes in regulating gene expression by means of the RNA interference pathway and may, in part, explain the evolutionary pressure to conserve argonaute-mediated catalysis in ..
  43. doi Current prospects for RNA interference-based therapies
    Beverly L Davidson
    Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    Nat Rev Genet 12:329-40. 2011
    b>RNA interference (RNAi) is a powerful approach for reducing expression of endogenously expressed proteins. It is widely used for biological applications and is being harnessed to silence mRNAs encoding pathogenic proteins for therapy...
  44. ncbi Argonaute2 is the catalytic engine of mammalian RNAi
    Jidong Liu
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Science 305:1437-41. 2004
    Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins...
  45. pmc The promises and pitfalls of RNA-interference-based therapeutics
    Daniela Castanotto
    Department of Molecular Biology and City of Hope Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA
    Nature 457:426-33. 2009
    ..base-pairing of small RNAs with messenger RNAs containing complementary sequence - a process known as RNA interference - has markedly advanced our understanding of eukaryotic gene regulation and function...
  46. pmc Interferon modulation of cellular microRNAs as an antiviral mechanism
    Irene M Pedersen
    Department of Molecular Biology, University of California San Diego, La Jolla, California 92093, USA
    Nature 449:919-22. 2007
    b>RNA interference through non-coding microRNAs (miRNAs) represents a vital component of the innate antiviral immune response in plants and invertebrate animals; however, a role for cellular miRNAs in the defence against viral infection in ..
  47. ncbi Transcriptional regulation of nanog by OCT4 and SOX2
    David J Rodda
    Stem Cell and Developmental Biology and Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672
    J Biol Chem 280:24731-7. 2005
    ..Furthermore, by specific knockdown of Oct4 and Sox2 mRNA by RNA interference in embryonic stem cells, we provide genetic evidence for a link between Oct4, Sox2, and the Nanog promoter...
  48. pmc Silencing of aphid genes by dsRNA feeding from plants
    Marco Pitino
    Department of Disease and Stress Biology, The John Innes Centre, Norwich Research Park, Norwich, United Kingdom
    PLoS ONE 6:e25709. 2011
    b>RNA interference (RNAi) is a valuable reverse genetics tool to study gene function in various organisms, including hemipteran insects such as aphids...
  49. doi A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity
    Na Yu Chia
    Gene Regulation Laboratory, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672
    Nature 468:316-20. 2010
    ..Here, we report a genome-wide RNA interference screen to identify genes which regulate self-renewal and pluripotency properties in hESCs...
  50. doi The many faces of RNAi
    Rene F Ketting
    Hubrecht Institute KNAW and University Medical Centre Utrecht, Utrecht, The Netherlands
    Dev Cell 20:148-61. 2011
    ..Although there is increased mechanistic understanding of the RNA interference (RNAi) pathways surrounding these small RNAs, how their effects are modulated by subcellular ..
  51. ncbi Small RNAs as big players in plant abiotic stress responses and nutrient deprivation
    Ramanjulu Sunkar
    Department of Biochemistry and Molecular Biology, 246 Noble Research Center, Oklahoma State University, Stillwater, OK 74078, USA
    Trends Plant Sci 12:301-9. 2007
    ..Subsequent studies have demonstrated an important functional role for these small RNAs in abiotic stress responses. This review focuses on recent advances, with emphasis on integration of small RNAs in stress regulatory networks...
  52. pmc Deep-sequencing of human Argonaute-associated small RNAs provides insight into miRNA sorting and reveals Argonaute association with RNA fragments of diverse origin
    Alexander Maxwell Burroughs
    Omics Science Center, RIKEN Yokohama Institute, Yokohama shi, Kanagawa, Japan
    RNA Biol 8:158-77. 2011
    ..Finally, we observe antisense miRNA transcripts are frequently present in low copy numbers across a range of diverse miRNA loci and these transcripts appear to associate with AGO proteins...
  53. pmc Deep sequencing of virus-infected cells reveals HIV-encoded small RNAs
    Nick C T Schopman
    Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, The Netherlands
    Nucleic Acids Res 40:414-27. 2012
    ..RNAs (viRNAs) play an important role in antiviral defence in plants, insects and nematodes by triggering the RNA interference (RNAi) pathway...
  54. doi Mechanisms of dsRNA uptake in insects and potential of RNAi for pest control: a review
    Hanneke Huvenne
    Laboratory of Agrozoology, Department of Crop Protection, Ghent University, Coupure Links 653, 9000 Ghent, Belgium
    J Insect Physiol 56:227-35. 2010
    b>RNA interference already proved its usefulness in functional genomic research on insects, but it also has considerable potential for the control of pest insects...
  55. pmc The crystal structure of human Argonaute2
    Nicole T Schirle
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 336:1037-40. 2012
    ..These results will enable structure-based approaches for harnessing the untapped therapeutic potential of RNA silencing in humans...
  56. pmc Antiviral RNA interference in mammalian cells
    P V Maillard
    Department of Biology, Swiss Federal Institute of Technology Zurich ETH Z, Zurich, Switzerland
    Science 342:235-8. 2013
    In antiviral RNA interference (RNAi), the DICER enzyme processes virus-derived double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that guide ARGONAUTE proteins to silence complementary viral RNA...
  57. pmc RNA interference functions as an antiviral immunity mechanism in mammals
    Yang Li
    Department of Plant Pathology and Microbiology, University of California, Riverside, CA 92521, USA
    Science 342:231-4. 2013
    Diverse eukaryotic hosts produce virus-derived small interfering RNAs (siRNAs) to direct antiviral immunity by RNA interference (RNAi). However, it remains unknown whether the mammalian RNAi pathway has a natural antiviral function...
  58. doi RNA-mediated chromatin-based silencing in plants
    Marjori Matzke
    Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Dr Bohr Gasse 3, A 1030 Vienna, Austria
    Curr Opin Cell Biol 21:367-76. 2009
    ..Two Pol II-related, plant-specific RNA polymerases, named Pol IV and Pol V, collaborate with proteins of the RNA interference machinery to generate long and short noncoding RNAs involved in epigenetic regulation...
  59. pmc An endogenous small interfering RNA pathway in Drosophila
    Benjamin Czech
    Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nature 453:798-802. 2008
    ..These observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles...
  60. pmc Selective blockade of microRNA processing by Lin28
    Srinivas R Viswanathan
    Stem Cell Program, Children s Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA
    Science 320:97-100. 2008
    ..Our results identify Lin28 as a negative regulator of miRNA biogenesis and suggest that Lin28 may play a central role in blocking miRNA-mediated differentiation in stem cells and in certain cancers...
  61. pmc Drosophila RNAi screen identifies host genes important for influenza virus replication
    Linhui Hao
    Institute for Molecular Virology, USA
    Nature 454:890-3. 2008
    ..Here we describe a novel genome-wide RNA interference (RNAi) screen in Drosophila that can be used to identify host genes important for influenza virus replication...
  62. pmc A genome-scale shRNA resource for transgenic RNAi in Drosophila
    Jian Quan Ni
    Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, Boston, Massachusetts, USA
    Nat Methods 8:405-7. 2011
    ..We show that shRNAs, modeled on an endogenous microRNA, are extremely effective at silencing gene expression during oogenesis. We also describe our progress toward building a genome-wide shRNA resource...
  63. pmc A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene
    Ji Luo
    Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cell 137:835-48. 2009
    ..Our results suggest a previously underappreciated role for Ras in mitotic progression and demonstrate a pharmacologically tractable pathway for the potential treatment of cancers harboring Ras mutations...
  64. pmc Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi
    Jodi L McBride
    Departments of Internal Medicine, Molecular Physiology and Biophysics, and Neurology, University of Iowa, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 105:5868-73. 2008
    ....
  65. doi Small RNA duplexes function as mobile silencing signals between plant cells
    Patrice Dunoyer
    Institut de Biologie Moleculaire des Plantes du CNRS, Université de Strasbourg 12 rue du Général Zimmer, 67084 Strasbourg Cedex, France
    Science 328:912-6. 2010
    In the plant RNA interference (RNAi) pathway, 21-nucleotide duplexes of small interfering RNA (siRNA) are processed from longer double-stranded RNA precursors by the RNaseIII Dicer-like 4 (DCL4)...
  66. pmc Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles
    Mark E Davis
    Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
    Nature 464:1067-70. 2010
    Therapeutics that are designed to engage RNA interference (RNAi) pathways have the potential to provide new, major ways of imparting therapy to patients...
  67. ncbi A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila
    Georg Dietzl
    Institute of Molecular Biotechnology of the Austrian Academy of Sciences IMBA, Dr Bohr Gasse 3 5, A 1030 Vienna, Austria
    Nature 448:151-6. 2007
    ..Our transgenic RNAi library thus opens up the prospect of systematically analysing gene functions in any tissue and at any stage of the Drosophila lifespan...
  68. pmc STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer
    Dimitrios Iliopoulos
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 39:493-506. 2010
    ..Thus, STAT3 is not only a downstream target of IL-6 but, with miR-21, miR-181b-1, PTEN, and CYLD, is part of the positive feedback loop that underlies the epigenetic switch that links inflammation to cancer...
  69. ncbi Structural basis for double-stranded RNA processing by Dicer
    Ian J Macrae
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Science 311:195-8. 2006
    The specialized ribonuclease Dicer initiates RNA interference by cleaving double-stranded RNA (dsRNA) substrates into small fragments about 25 nucleotides in length...
  70. pmc Functional genomic screen reveals genes involved in lipid-droplet formation and utilization
    Yi Guo
    Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA
    Nature 453:657-61. 2008
    ..Here we show, by means of a genome-wide RNA interference (RNAi) screen in Drosophila S2 cells that about 1...
  71. ncbi Control of coleopteran insect pests through RNA interference
    James A Baum
    Monsanto Company, 700 Chesterfield Parkway West, Chesterfield, Missouri 63017 1732, USA
    Nat Biotechnol 25:1322-6. 2007
    ..this end, we demonstrate that ingestion of double-stranded (ds)RNAs supplied in an artificial diet triggers RNA interference in several coleopteran species, most notably the western corn rootworm (WCR) Diabrotica virgifera virgifera ..
  72. pmc Systematic analysis of human protein complexes identifies chromosome segregation proteins
    James R A Hutchins
    Research Institute of Molecular Pathology IMP, Dr Bohr Gasse 7, A 1030 Vienna, Austria
    Science 328:593-9. 2010
    ..Results from recent RNA interference screens indicate that the identity and composition of these protein complexes is incompletely understood...
  73. pmc Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells
    Megha Ghildiyal
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Science 320:1077-81. 2008
    Small interfering RNAs (siRNAs) direct RNA interference (RNAi) in eukaryotes. In flies, somatic cells produce siRNAs from exogenous double-stranded RNA (dsRNA) as a defense against viral infection...
  74. ncbi Genome-wide RNAi screening in Caenorhabditis elegans
    Ravi S Kamath
    Wellcome Trust Cancer Research UK Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK
    Methods 30:313-21. 2003
    ..in the specific inactivation of an endogenous gene with corresponding sequence; this technique is known as RNA interference (RNAi)...
  75. pmc Functional genomics reveal that the serine synthesis pathway is essential in breast cancer
    Richard Possemato
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 476:346-50. 2011
    ..b>RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting ..
  76. doi Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells
    Claudia Scholl
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Cell 137:821-34. 2009
    ..We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS, the most commonly ..
  77. pmc Lifespan regulation by evolutionarily conserved genes essential for viability
    Sean P Curran
    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
    PLoS Genet 3:e56. 2007
    ..These results suggest that insulin-signaling pathways play a role in regulation of aging at any stage in life...
  78. pmc TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing
    Astrid D Haase
    Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4508 Basel, Switzerland
    EMBO Rep 6:961-7. 2005
    Dicer is a key enzyme involved in RNA interference (RNAi) and microRNA (miRNA) pathways. It is required for biogenesis of miRNAs and small interfering RNAs (siRNAs), and also has a role in the effector steps of RNA silencing...
  79. pmc The Aedes aegypti toll pathway controls dengue virus infection
    Zhiyong Xi
    W Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
    PLoS Pathog 4:e1000098. 2008
    ..which appears to utilize different immune pathways against different types of viruses, in addition to an RNA interference-based defense system. We have used the recently released whole-genome sequence of the Ae...
  80. doi Molecular mechanisms of RNA interference
    Ross C Wilson
    Howard Hughes Medical Institute
    Annu Rev Biophys 42:217-39. 2013
    ..Molecular structures of Dicer and Argonaute proteins, and of RNA-bound complexes, have offered exciting insights into the mechanisms operating at the heart of RNA-silencing pathways...
  81. ncbi Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
    Coleen T Murphy
    Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143 2200, USA
    Nature 424:277-83. 2003
    ....
  82. ncbi Autophagy genes are essential for dauer development and life-span extension in C. elegans
    Alicia Melendez
    Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA
    Science 301:1387-91. 2003
    ..elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans...
  83. ncbi Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry
    Matthew J Evans
    Center for the Study of Hepatitis C, The Rockefeller University, 1230 York Ave, New York 10021, USA
    Nature 446:801-5. 2007
    ..With CLDN1 we have identified a novel key factor for HCV entry and a new target for antiviral drug development...
  84. doi Viral suppressors of RNA silencing
    Jozsef Burgyan
    Istituto di Virologia Vegetale, CNR, Strada delle Cacce 73, Torino, Italy
    Trends Plant Sci 16:265-72. 2011
    ..This review highlights the current understanding of and new insights into the mechanisms and functions of plant VSRs...
  85. ncbi Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis
    Qing Zhong
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75390, USA
    Cell 121:1085-95. 2005
    ..Elimination of Mule expression by RNA interference stabilizes Mcl-1 protein, resulting in an attenuation of the apoptosis induced by DNA-damage agents...
  86. pmc RNA therapeutics: beyond RNA interference and antisense oligonucleotides
    Ryszard Kole
    AVI BioPharma, 3450 Monte Villa Parkway, Bothell, Washington 98021, USA
    Nat Rev Drug Discov 11:125-40. 2012
    ..b>RNA interference and antisense oligonucleotides downregulate gene expression by inducing enzyme-dependent degradation of ..
  87. doi Widespread translational inhibition by plant miRNAs and siRNAs
    Peter Brodersen
    Institut de Biologie Moleculaire des Plantes du CNRS, Unité Propre de Recherche 2357, 12 rue du Général Zimmer, 67084 Strasbourg Cedex, France
    Science 320:1185-90. 2008
    ..Also as in animals, the decapping component VARICOSE (VCS)/Ge-1 is required for translational repression by miRNAs, which suggests that the underlying mechanisms in the two kingdoms are related...
  88. ncbi Role of histone H3 lysine 27 methylation in Polycomb-group silencing
    Ru Cao
    Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7295, USA
    Science 298:1039-43. 2002
    ..Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing...
  89. pmc An endogenous, systemic RNAi pathway in plants
    Patrice Dunoyer
    Institut de Biologie Moleculaire des Plantes du CNRS, UPR2357, Universite de Strasbourg, Strasbourg Cedex, France
    EMBO J 29:1699-712. 2010
    ..existence of an endogenous RNA-silencing pathway that functionally recapitulates the effects of experimental RNA interference (RNAi) used for gene knockdown in organisms such as Caenorhabditis elegans and Drosophila...
  90. ncbi CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members
    Eirini Trompouki
    Institute of Immunology, Biomedical Sciences Research Center Alexander Fleming, 34 Alexander Fleming Street, Vari 16672, Greece
    Nature 424:793-6. 2003
    ..These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappaB that is required for appropriate cellular homeostasis of skin appendages...
  91. pmc The role of RNAi and microRNAs in animal virus replication and antiviral immunity
    Jennifer L Umbach
    Department of Molecular Genetics and Microbiology and Center for Virology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Genes Dev 23:1151-64. 2009
    ..Insights derived from this research will facilitate a better understanding of viral pathogenesis and the host innate immune response to viral infection...
  92. doi On the road to reading the RNA-interference code
    Haruhiko Siomi
    Department of Molecular Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku ku, Tokyo 160 8582, Japan
    Nature 457:396-404. 2009
    ..This process, known as RNA interference (RNAi) or RNA silencing, involves small non-coding RNAs, which associate with nuclease-containing regulatory ..
  93. doi RNA interference in Lepidoptera: an overview of successful and unsuccessful studies and implications for experimental design
    Olle Terenius
    Department of Ecology, Swedish University of Agricultural Sciences, Uppsala, Sweden
    J Insect Physiol 57:231-45. 2011
    Gene silencing through RNA interference (RNAi) has revolutionized the study of gene function, particularly in non-model insects. However, in Lepidoptera (moths and butterflies) RNAi has many times proven to be difficult to achieve...
  94. pmc An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles
    Christine M Clemson
    University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655, USA
    Mol Cell 33:717-26. 2009
    ..Collectively, results demonstrate that NEAT1 functions as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the foundation of a nuclear domain...
  95. pmc Cucumber mosaic virus-encoded 2b suppressor inhibits Arabidopsis Argonaute1 cleavage activity to counter plant defense
    Xiuren Zhang
    Laboratory of Plant Molecular Biology, Rockefeller University, New York, New York 10021, USA
    Genes Dev 20:3255-68. 2006
    ..These findings provide insight on the molecular arms race between host antiviral RNA silencing and virus counterdefense...
  96. ncbi Identification of virus-encoded microRNAs
    Sebastien Pfeffer
    Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, Box 186, New York, NY 10021, USA
    Science 304:734-6. 2004
    ..Given that miRNAs function in RNA silencing pathways either by targeting messenger RNAs for degradation or by repressing translation, we identified viral regulators of host and/or viral gene expression...
  97. ncbi Histone demethylation mediated by the nuclear amine oxidase homolog LSD1
    Yujiang Shi
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Cell 119:941-53. 2004
    ..The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases...
  98. ncbi The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells
    Yuin Han Loh
    Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672
    Nat Genet 38:431-40. 2006
    ..By integrating RNA interference-mediated depletion of Oct4 and Nanog with microarray expression profiling, we demonstrated that these factors ..
  99. pmc Noncoding flavivirus RNA displays RNA interference suppressor activity in insect and Mammalian cells
    Esther Schnettler
    Laboratory of Virology, Wageningen University, Wageningen, Netherlands
    J Virol 86:13486-500. 2012
    ..b>RNA interference (RNAi) is the predominant antiviral response against invading RNA viruses in insects and plants...
  100. ncbi Heterochromatin revisited
    Shiv I S Grewal
    Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Genet 8:35-46. 2007
    ....
  101. pmc Discovery of insect and human dengue virus host factors
    October M Sessions
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Nature 458:1047-50. 2009
    ..Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library...

Research Grants80

  1. Mapping for Specialized Domains for FCeRI Signaling &Internalization
    Bridget S Wilson; Fiscal Year: 2013
    ..We will use RNA interference and transient transfection methods to disrupt the spectrin cortical network...
  2. Ligand Directed Transdermal siRNA Delivery to Improve Wound Healing
    David M Evans; Fiscal Year: 2012
    ..Using RNA interference (RNAi) to down regulate a target gene expression, we have previously demonstrated that a multi-targeted siRNA ..
  3. Genetics and Haloperidol Response
    Robert J Hitzemann; Fiscal Year: 2012
    ..of the QTL and network based approaches using all possible methods but emphasizing viral mediated transfer of RNA interference. This project has been funded by the VA Merit system since 1991;the original project began with the idea that ..
  4. Genomics of Antiviral Responses of Anopheles gambiae Against O'nyong-nyong Virus
    Young S Hong; Fiscal Year: 2010
    ..In ONNV- infected An. gambiae, hsc-70B expression was found to be highly induced, and RNA interference (RNAi) gene- silencing of hsc-70B increased ONNV titers in the mosquito...
  5. Regulation of microRNA-375 by cyclic-AMP in pancreatic beta-cells
    DAVID MATTHEW KELLER; Fiscal Year: 2010
    ..MicroRNAs hybridize with target genes and repress protein synthesis via an RNA interference (RNAi) mechanism (He and Hannon, 2004;Meister and Tuschl, 2004;Novina and Sharp, 2004;Siomi and Siomi, 2009)...
  6. Sex Steroid Hormone Regulation of Drug Reinforcement
    Diane Lebesgue; Fiscal Year: 2012
    ..then assess E2/G1 modulation of cocaine reinforcement in animals subjected to GPR30 knockdown using in vivo RNA interference targeted to the VTA...
  7. Inhibiting Mucosal HIV-1 Transmission by Host Cell RNA Interference
    Alexandra L Howell; Fiscal Year: 2013
    ..We propose to use RNA interference (RNAi) with short-interfering RNA (siRNA) to silence expression of CCR5 and DC-SIGN on mucosal leukocytes ..
  8. Regulation of NFkappaB activity by the Estrogen Receptor
    Kendall W Nettles; Fiscal Year: 2012
    ..to the MCP-1, IL-6, IL-8, MIP-1 and TNF-a genes by chromatin immunoprecipitation, and assay the effects of RNA interference targeting CBP and Grip1 on expression of the same genes...
  9. Potential Mechanisms of Glucagon-like peptide-1 in Fatty Liver Disease
    Frank A Anania; Fiscal Year: 2010
    ..Specific Aim 2: To employ RNA interference for GLP-1 receptor and determine whether the gene profile associated with GLP-1, which favors hepatocyte ..
  10. Interaction between RNA interference and RNA editing pathways
    Kazuko Nishikura; Fiscal Year: 2013
    ..Our research focuses also on apoptosis, which is highly relevant to many human diseases including cancer. ..
  11. Knockdown of Gene Expression in Immune Cells in Humanized Mice
    Judy Lieberman; Fiscal Year: 2010
    ..Two recent technologies, RNA interference (RNAi) and humanized mice with robust functional human immune responses, now provide an opportunity for ..
  12. Histone Chaperones in Angiogenesis
    Soumen Paul; Fiscal Year: 2012
    ..Intriguingly, knockdown of HIRA by RNA interference (RNAi) in endothelial cells inhibits angiogenic signal-induced induction of Vegfr1 and other angiogenesis ..
  13. Analysis of epigenetic regulation in early mammalian embryos via RNA interference
    Charles R Long; Fiscal Year: 2010
    ..We will test our hypothesis by using RNA interference to study the functional genomics of epigenetic reprogramming in an established model of in vitro embryo ..
  14. Roles of RNA Polymerases IV and V in siRNA-mediated gene silencing
    CRAIG STUART PIKAARD; Fiscal Year: 2013
    ..in multiple human diseases and genetic disorders, including cancer, and targeted gene silencing using small RNA interference (RNAi) technologies are being used in medical and agricultural biotechnology applications...
  15. A Ribozyme Rescue Strategy for Dry Age-Related Macular Degeneration
    John M Sullivan; Fiscal Year: 2013
    ..The objective of the proposed experiments is to use hammerhead ribozymes (hhRz) or RNA interference (shRNA) as genetic tools to knockdown (KD) expression of key proteins in rod PRs or RPE cells that ..
  16. Mechanisms of innate immune response modulation by mechanical ventilation
    William A Altemeier; Fiscal Year: 2012
    ..ventilation, (b) inhibiting AP-1 activation during mechanical ventilation and LPS exposure, and (c) using RNA interference to determine the function of specific AP-1 subunits identified in (a)...
  17. Regulation of apoptosis by PI 3-kinase/Akt signaling
    Geoffrey M Cooper; Fiscal Year: 2012
    ..NF[unreadable]B and NFAT transcription factors will be investigated by chromatin immunoprecipitation and RNA interference. Computational analysis will be expanded to identify transcription factor binding sites in predicted ..
  18. Role of Matrix Metalloproteinase-1 in Endothelial Cell Senescence
    Catherine D Mao; Fiscal Year: 2010
    ..in presence of MMP-1 and in absence of MMP1 activity and expression using specific inhibitors and small RNA interference respectively, and ii) by analyzing the activation of PAR-1 in response to lithium and its dependency on MMP-1 ..
  19. Chemoprevention of urinary bladder carcinogenesis by flavokawain A
    Xiaolin Zi; Fiscal Year: 2012
    ..will validate these targets by examining their expression in vivo in these tested animal models and by using RNA interference and overexpression vectors to determine their contributions to flavokawain A's action in vitro, as well ..
  20. RNA interference therapy for Huntington's disease: studies in non-human primates
    Beverly L Davidson; Fiscal Year: 2010
    ..challenge set forth in the RFA is to extend the current understanding of the feasibility and safety of RNA interference (RNAi) therapeutics for the treatment of chronic neurological disorders from rodent models of disease to a ..
  21. Genomic adaptation to HIV infection of the CNS in opioid-abusers
    Rajnish S Dave; Fiscal Year: 2012
    ..Such genomic adaptation involves RNA interference (RNAi) and is mediated by microRNA (miRNA)...
  22. Iron, NO, and Lipid Peroxide in Photodynamic Therapy
    ALBERT GIROTTI; Fiscal Year: 2013
    ..irradiation, and apoptosis evaluation;use of NOS inhibitors, NO scavengers, and chemical NO donors;RNA interference;immunoblotting;confocal microscopy;and PDT of human tumors implanted in immunosuppressed mice;in addition to ..
  23. MECHANISMS OF DENDRITE MORPHOGENESIS BY THE ANAPHASE-PROMOTING COMPLEX
    ALBERT HONG JAE KIM; Fiscal Year: 2013
    ..These experiments will use a rigorous RNA interference- based approach to determine the mechanism of S5a-driven dendrite morphogenesis and utilize a novel cellular ..
  24. Prostaglandin signaling following seizures
    Jianxiong Jiang; Fiscal Year: 2013
    ..I will also receive training from Dr. Kerry Ressler for lentiviral-mediated RNA interference in the mouse hippocampus, take courses on advanced neuroscience techniques, research ethics and lab ..
  25. Arsenic, Histone Modification, and Transcription
    LYNN SHELDON; Fiscal Year: 2009
    ..associated proteins in Specific Aim II with transcriptional activation, the identified proteins will be tested in cells in vivo in RNA interference (RNAi) analyses and in vitro enzyme activity assays (Specific Aim III).
  26. Preclinical testing of a novel PDK1 inhibitor for treating vestibular schwannoma
    Abraham Jacob; Fiscal Year: 2013
    ..assays, flow cytometry, TUNEL, antibody arrays, caspase activity assays, proliferation indices, FACS, RNA interference, PCR and Western blots), we plan to better understand the end biologic effects of decreased AKT signaling on ..
  27. CELLULAR REGULATION OF CLATHRIN ASSEMBLY AND FUNCTION
    Frances M Brodsky; Fiscal Year: 2013
    ..The experimental approaches to these studies include protein crystallography and structure-based mutagenesis, RNA interference, membrane traffic and migration assays, and gene targeting strategies to produce animals that can be ..
  28. ROLE OF COREGULATORS IN STEROID HORMONE-REGULATED TRANSCRIPTION
    Michael R Stallcup; Fiscal Year: 2013
    ..This will be done by using RNA interference to systematically deplete the endogenous levels of selected coregulators, followed by chromatin ..
  29. A XENOPUS LAEVIS RESEARCH RESOURCE FOR IMMUNOBIOLOGY
    Jacques Robert; Fiscal Year: 2013
    ..g., thymus, spleen) or leukocytes;by developing in vivo knockdown by RNA interference using transgenesis to reveal the function of immunologically-relevant genes;and by generating new X...
  30. Ribosomal Protein Gene Silencing in Neural Crest Stem Cells
    JOHNSON MING YU LIU; Fiscal Year: 2010
    ..Further, we propose that RNA interference (RNAi) could be used to reduce the amount of free Rpl11 in cells haploinsufficient for RPL5 with consequent ..
  31. Microfluidic-microtiter interface for rapid large-scale screenings of C. elegans
    Adela Ben Yakar; Fiscal Year: 2010
    ..elegans by RNA interference (RNAi)...
  32. Functional Analysis of the Embryonic Epigenome in a Non-rodent Model
    Mark E Westhusin; Fiscal Year: 2013
    ..For study 1, RNA interference (RNAi) will be used transiently "knock down" expression of DNMTs and HMTs at the 1-cell stage of development...
  33. Characterization of Genetic Abnormalities in MDS and Their Clinical Impact
    Rafael Bejar; Fiscal Year: 2013
    ..In collaboration with Dr. David Root from the RNAi Consortium at the Broad Institute, a pooled short hairpin RNA interference screen in human CD34+ hematopoietic cells will be performed...
  34. Investigating the pathogenesis of CoQ10 deficiencies
    Catarina M Quinzii; Fiscal Year: 2013
    ..degrees of CoQ10 deficiency in the same genetic background, she will modulate COQ2 and PDSS2 expression using RNA interference (RNAi)...
  35. HEPATIC DEGRADATION OF CYTOCHROME P450 ENZYMES
    Maria Almira Correia; Fiscal Year: 2013
    ....
  36. Tick Midgut Proteins Critical for Borrelia Transmission
    Sukanya Narasimhan; Fiscal Year: 2010
    ..b>RNA interference technique will be exploited to determine if the interaction facilitates the events that precede transmission ..
  37. Epigenetic regulation of stem cell senescence in aging
    DAVID TOCHUKWU ASUZU; Fiscal Year: 2011
    ..signaling and its epigenetic control by polycomb proteins using real-time RT-PCR, Western immunoblotting and RNA interference. Results from this project may reveal new therapeutic targets to restore ICC stem cells and improve GI health ..
  38. A Novel Model of, and Pre-clinical Therapy for, Scleroderma Lung Disease
    Sergei P Atamas; Fiscal Year: 2012
    ..the efficacy of hIL-442-blocking monoclonal antibodies, and blockade of human IL-442 production through RNA interference. These experiments will form basis for future clinical trials targeting IL-442 in humans...
  39. Modeling schizophrenia gamma deficits using cell-specific RNAi knockdown of GAD67
    RITCHIE EDWARD BROWN; Fiscal Year: 2012
    ..In order to specifically knockdown (KD) gene expression we propose to use RNA interference (RNAi), building on our previous experience using this technique in the sleep field...
  40. The role of satellite rasiRNA in the Segregation Distorter system of Drosophila
    AMANDA MARIE LARRACUENTE; Fiscal Year: 2013
    ..The mechanism behind SD is unknown but it may involve RNA interference (RNAi), similar to other meiotic driver systems...
  41. Molecular Mechanisms of Ion Channels in T Lymphocytes
    Michael D Cahalan; Fiscal Year: 2013
    ..The channels that underlie SOCE have been identified recently through RNA interference (RNAi) screening as a conserved family of four transmembrane-spanning proteins named Orai that are activated ..
  42. Surgical Wound Repair: Role of A Neuroendothelial Axis
    NICOLE SIMONE GIBRAN; Fiscal Year: 2010
    ..We will use RNA interference to deplete the neurokinin 1 receptor...
  43. Control of Cardiogenesis by microRNA Editing
    Kazuko Nishikura; Fiscal Year: 2010
    ..The miRNA-mediated RNA interference recently emerged as a previously unsuspected mechanism to regulate cardiogenesis during development...
  44. Molecular Physiology of the Epitrachael Endocrine System
    Michael E Adams; Fiscal Year: 2012
    ..Results of these studies also may provide basic new information about vector-borne human diseases involving mosquitoes, flies, ticks, and other arthropods. ..
  45. Cyclin-Dependent Kinase Inhibition During S Phase
    Geoffrey I Shapiro; Fiscal Year: 2013
    ..Finally, RNA interference screens will be used to define novel targets in DNA damage and other pathways, depletion of which may augment ..
  46. Ligands and cofactors required for RORgt function in the immune system
    Dan Littman; Fiscal Year: 2013
    ..transcriptional activity in Drosophila S2 cells, and have exploited this observation to perform a genome-wide RNA interference screen...
  47. STRUCTURE AND FUNCTION OF PAXILLIN
    Christopher E Turner; Fiscal Year: 2012
    ..To accomplish these goals, we will suppress endogenous protein expression by RNA interference or express mutant proteins in fibroblasts and utilize confocal fluorescence time-lapse microscopy, combined ..
  48. Screen for Small Molecule Regulators of Retinal Progenitor Epithelial Cell Phagoc
    CHARLES YOON HYUNG CHO; Fiscal Year: 2010
    ..Reduction in the levels of MERTK by RNA interference resulted in a decrease in phagocytic activity providing a cellular phenocopy of a core cell biological event ..
  49. Structures of RNA processing and Silencing Enzymes in Prokaryotes
    Hong Li; Fiscal Year: 2013
    ..The proposed molecular mechanisms of this novel pathway may be exploited for building specific immunity against undesirable genetic elements such as those spreading antibiotics resistance genes. ..
  50. Reactivation of Fetal Gamma-globin Genes for the Treatment of Beta-globin Disorde
    Osamu Tanabe; Fiscal Year: 2010
    ..RNA (siRNA) duplexes that specifically knock-down TR2, TR4, or their potential co-regulatory proteins by RNA interference. The second strategy will be to identify low-molecular-weight chemical ligands, either synthetic or natural, ..
  51. Analysis of NKLAM: A Novel Gene Associated With Cellular Cytotoxicity
    Jacki Kornbluth; Fiscal Year: 2013
    ..To test this, RNA interference (RNAi) was used to down-regulate UCKL-1 expression in NK-sensitive K562 erythroleukemia cells and other NK ..
  52. MOLECULAR MODELS OF IMMUNE-MEDIATED VASCULAR INJURY
    Jeffrey R Bender; Fiscal Year: 2012
    ..MAPK-activated protein kinase 2 (MK2) and novel, T cell-specific MK2 targets, using pharmacologic inhibitors, RNA interference (RNAi)-based approaches, T cells from relevant gene-deleted mice, and screens for T cell Hsp27 homologues;(2) ..
  53. Defining the telomerase holoenzyme in progenitor cells with aging
    Steven E Artandi; Fiscal Year: 2013
    ..Depletion of TCAB1 in human cells using RNA interference prevents telomerase from localizing in Cajal bodies and leads to profound telomere shortening...
  54. RNA CONFORMATION AND CATALYSIS
    David P Bartel; Fiscal Year: 2013
    ..The experiments of this proposal focus on the mechanism, biology, and evolution of RNA interference (RNAi), an example of a structure-dependent function in which double-stranded RNA (dsRNA) triggers the ..
  55. PHOSPHOPEPTIDE METABOLISM IN ADIPOCYTES
    Joseph Avruch; Fiscal Year: 2013
    ..In AIM2 we will use genome-wide RNA interference to generate a catalog of cellular components required for the ability of mTORC1 to promote phosphorylation of ..
  56. SPLICING OF MRNA PRECURSORS
    Michael R Green; Fiscal Year: 2013
    ..In addition, we will perform genome-wide loss-of-function RNA interference screens to study mechanisms of splicing repression and to identify new splicing repressors...
  57. Cholinergic Receptors as Targets for Accelerated Anthelmintic Discovery
    MICHAEL JOHN KIMBER; Fiscal Year: 2013
    ..The experiments will combine bioimaging techniques, RNA interference (RNAi), bioassays, physiology and pharmacology to determine which of these receptors will progress to the ..
  58. Obesity and diabetes genetics in Caenorhabditis elegans.
    Alexander A Soukas; Fiscal Year: 2013
    ..The investigator will learn to apply genomics (RNA interference, whole-genome sequencing, high-throughput technology), forward genetics, and biochemistry 1) to identify new ..
  59. Role of Natural Killer Lytic-Associated Molecule (NKLAM) in Natural Killer Functi
    Jacki Kornbluth; Fiscal Year: 2010
    ..b>RNA interference was used to downregulate UCKL-1 expression in K562 erythroleukemia cells...
  60. Histoplasma Gene Expression and Organism Persistence
    ALAN GEORGE SMULIAN; Fiscal Year: 2012
    ..Using RNA interference (RNAi) and microarray analysis, it will be determined if impaired persistence results from an inability to ..
  61. MAP Kinase Phosphatase 3 (MKP-3) and Obesity-related Gluconeogenesis
    Haiyan Xu; Fiscal Year: 2013
    ..Reduction of MKP-3 expression by RNA interference decreases gluconeogenesis in hepatocytes and lowers fasting blood glucose levels in obese mice...
  62. SECRETION AND BIOSYNTHESIS OF INSULIN
    Michael L McDaniel; Fiscal Year: 2012
    ..transition pore (MTP) &nitric oxide (NO) are required for GSK-3 &mTOR signaling by A) examining if RNA interference of nitric oxide synthase (NOS) isoforms or MTP components, VDAC &ANT, alter the physiological responses ..
  63. DC-SIGN Inhibitors for the Treatment of HIV Infection
    ALLEN BERNARD REITZ; Fiscal Year: 2013
    ..Both RNA interference and carbohydrate-binding agents have been shown as potential means to inhibit DC-SIGN-mediated transmission ..
  64. Molecular Mechanism of cell-cell spread of Listeria in polarized epithelial cells
    KEITH PATRICK IRETON; Fiscal Year: 2013
    ..including immunofluorescence microscopy, evaluation of ERM protein phosphorylation through Western blotting, RNA interference to investigate the function of Tuba and its ligands in spreading, and virulence studies using mice...
  65. Regulation and Function of Urocortins and their Receptors
    Aditi Bhargava; Fiscal Year: 2013
    ..To define the contributions of colon-specific Ucns and CRFRs in intestinal inflammation using RNA interference (RNAi)...
  66. Mechanisms of Sequence-Based Resistance to Viruses and Plasmids in Eubacteria
    Erik J Sontheimer; Fiscal Year: 2010
    ..The best known of these mechanisms, RNA interference, uses double-stranded RNA to trigger the silencing of specific genes...
  67. Does Dengue Virus Suppress RNA Interference in its Mosquito Vector?
    KATHRYN ALYCE HANLEY; Fiscal Year: 2010
    ..the front-line defense against viruses is the interferon (IFN) response, whereas in many arthropods, it is RNA interference (RNAi), the targeted destruction of messenger-sense RNA with homology to a double-stranded RNA trigger...
  68. The Role of RNA Interference in West Nile Virus Diversification
    Douglas E Brackney; Fiscal Year: 2010
    ..respond to viral infections mainly via type-1 interferon and natural killer cells, whereas mosquitoes rely on RNA interference (RNAi) as an intracellular defense mechanism to control viral infections...
  69. Photoreceptors Involved in Chlamydomonas reinhardtii Circadian Entrainment
    SIGRID JACOBSHAGEN; Fiscal Year: 2007
    ..a particular photoreceptor is involved in entrainment, knockout strains with no photoreceptor protein or RNA interference strains with reduced photoreceptor levels will be tested for impaired abilities to phase shift upon light ..
  70. HK polymers as transfection reagents for siRNA delivery
    Frank Xie; Fiscal Year: 2005
    ..b>RNA interference (RNAi) is a process of sequence-specific gene silencing mediated by double-stranded RNA-molecules...
  71. A Novel Epigenetic Gene Silencing Technology
    MING MING contact ZHOU; Fiscal Year: 2010
    ..b>RNA interference (RNAi) that blocks gene translation to protein by small interfering RNA (siRNA)-triggered messenger RNA ..
  72. ENDOCANNABINOID ANALGESIA: AN IN VIVO GENE TRANSFER - LIPIDOMICS APPROACH
    Andrea Hohmann; Fiscal Year: 2007
    ..Successful validation of our technological approach and hypotheses may facilitate development of endocannabinoid-based pharmacological and gene therapies for pain. [unreadable] [unreadable] [unreadable]..
  73. RNA-Mediated Silencing: Mechanisms and Biological Roles in Chlamydomonas
    Heriberto Cerutti; Fiscal Year: 2009
    ..The RNA interference machinery has also been implicated in the processing and function of microRNAs, a class of small RNAs that ..
  74. Regulation of caspase-1 by Sod2 in the heart
    Kumuda C Das; Fiscal Year: 2010
    ..We recently made the novel observation that downregulation of basal level of MnSOD (also known as Sod2) by RNA interference upregulated caspase-1 expression in microvascular endothelial cells (EC)...
  75. Role of Polyamine Oxidase in Apoptosis Studies with RNA Interference
    GLENN KUEHN; Fiscal Year: 2009
    ..The origin of the H2O2 is not known. In preliminary studies, we have applied RNA interference (RNAi) methods, using a newly discovered, rapid technique for introducing double-stranded (dsRNA) into plants ..
  76. RNA INTERFERENCE AS A WEAPON AGAINST BIOTERRORISM
    Judy Lieberman; Fiscal Year: 2007
    b>RNA interference (RNAi) is a powerful mechanism of post-transcriptional gene silencing originally described in plants and invertebrates as part of an ancient defense for protection against viruses and genetic damage from transposable ..
  77. RNAi therapy for Huntingtons disease: safety & efficacy in the nonhuman primate
    Jodi L McBride; Fiscal Year: 2010
    ..b>RNA interference (RNAi) has recently emerged as a leading candidate approach to reduce expression of disease genes by ..
  78. Small Interfering RNAs: Inhibition of Oral Carcinogenesis in a Mouse Model
    Lorraine J Gudas; Fiscal Year: 2010
    ..Therefore, new approaches for the prevention and therapy of human oral cancer are needed. RNA interference (RNAi) inhibits gene expression by degrading specific mRNAs...
  79. Silencing Suppression Mechanism of a Herpes Simplex Virus Virion Component
    NIL CELEBI CHERUKURI; Fiscal Year: 2009
    ....
  80. Inhibition of Collagen Synthesis by RNA Interference
    Kyonggeun Yoon; Fiscal Year: 2003
    ..diseases, we propose to inhibit the type I collagen synthesis using a novel strategy of gene silencing by RNA interference (RNAi)...