small interfering rna

Summary

Summary: Small ANTISENSE RNAs (20 -25 nucleotides) that are generated from specific dsRNAs (RNA, DOUBLE-STRANDED) which trigger targeted mRNA (RNA, MESSENGER) degradation (RNA INTERFERENCE). They serve as guides for the cleavage of homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. The same ribonuclease, Dicer, that is required for processing of the dsRNAs to siRNA is also involved in processing MICRORNAS (miRNAs) from their precursor RNAs.

Top Publications

  1. ncbi MicroRNAs: genomics, biogenesis, mechanism, and function
    David P Bartel
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 116:281-97. 2004
  2. 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
  3. ncbi MicroRNAs: small RNAs with a big role in gene regulation
    Lin He
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 5:522-31. 2004
  4. 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
  5. ncbi Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs
    Gunter Meister
    Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, Box 186, New York, NY 10021, USA
    Mol Cell 15:185-97. 2004
  6. pmc Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5' terminal nucleotide
    Shijun Mi
    National Institute of Biological Sciences, No 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China
    Cell 133:116-27. 2008
  7. pmc Arabidopsis ARGONAUTE1 is an RNA Slicer that selectively recruits microRNAs and short interfering RNAs
    N Baumberger
    Sainsbury Laboratory, Norwich Research Park, Norwich NR4 7UH, United Kingdom
    Proc Natl Acad Sci U S A 102:11928-33. 2005
  8. ncbi Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis
    Jing Yang
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Cell 117:927-39. 2004
  9. 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
  10. 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

Research Grants

  1. TIMOTHY L SITA; Fiscal Year: 2016
  2. Novel genomic effects of Y-linked polymorphisms
    Daniel L Hartl; Fiscal Year: 2012
  3. Margot S Damaser; Fiscal Year: 2014
  4. Role of estrogen-related receptors in cardiac and skeletal muscle
    Janice M Huss; Fiscal Year: 2010
  5. Hepatocarcinogenesis Secondary to Hepatitis C
    Srikanta Dash; Fiscal Year: 2012
  6. Reactivation of Fetal Gamma-globin Genes for the Treatment of Beta-globin Disorde
    Osamu Tanabe; Fiscal Year: 2010
  7. Zhenfeng Duan; Fiscal Year: 2014
  8. Robert W McCarley; Fiscal Year: 2016
  9. A Novel Epigenetic Gene Silencing Technology
    MING MING contact ZHOU; Fiscal Year: 2010
  10. The new biology of estrogen action in aromatase resistance breast cancer cells
    JOAN SUEDEE LEWIS-WAMBI; Fiscal Year: 2011

Detail Information

Publications435 found, 100 shown here

  1. ncbi MicroRNAs: genomics, biogenesis, mechanism, and function
    David P Bartel
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
    Cell 116:281-97. 2004
    ..Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes...
  2. 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
    HIV-1 exploits multiple host proteins during infection. We performed a large-scale small interfering RNA screen to identify host factors required by HIV-1 and identified more than 250 HIV-dependency factors (HDFs)...
  3. ncbi MicroRNAs: small RNAs with a big role in gene regulation
    Lin He
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 5:522-31. 2004
  4. 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
    ..Importantly, ATP is not required for miRNA processing, RISC assembly, or multiple rounds of target-RNA cleavage. These results define the composition of RISC and demonstrate that miRNA processing and target-RNA cleavage are coupled...
  5. ncbi Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs
    Gunter Meister
    Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, Box 186, New York, NY 10021, USA
    Mol Cell 15:185-97. 2004
    ..The specific role of Ago2 in guiding target RNA cleavage was confirmed independently by siRNA-based depletion of individual Ago members in combination with a sensitive positive-readout reporter assay...
  6. pmc Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5' terminal nucleotide
    Shijun Mi
    National Institute of Biological Sciences, No 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China
    Cell 133:116-27. 2008
    ..This suggests that specialization of AGO complexes might involve remodeling the 5' end-binding pocket to accept certain small RNA sequences, perhaps explaining the evolutionary drive for miRNAs to initiate with uridine...
  7. pmc Arabidopsis ARGONAUTE1 is an RNA Slicer that selectively recruits microRNAs and short interfering RNAs
    N Baumberger
    Sainsbury Laboratory, Norwich Research Park, Norwich NR4 7UH, United Kingdom
    Proc Natl Acad Sci U S A 102:11928-33. 2005
    ..Based on sequence similarity, we predict that other Arabidopsis AGOs might have a similar catalytic activity but recruit different subsets of siRNAs or miRNAs...
  8. ncbi Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis
    Jing Yang
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Cell 117:927-39. 2004
    ..These results establish a mechanistic link between Twist, EMT, and tumor metastasis...
  9. 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...
  10. 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
    ..Interestingly, target RNA cleavage can be rescued if an otherwise non-cleavable passenger strand shows a nick at the scissile phosphodiester bond, which further indicates that the cleavage event per se is not essential...
  11. ncbi A microRNA in a multiple-turnover RNAi enzyme complex
    Gyorgy Hutvagner
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, Room 825, 364 Plantation Street, Worcester, MA 01605, USA
    Science 297:2056-60. 2002
    ..Each let-7-containing complex directs multiple rounds of RNA cleavage, which explains the remarkable efficiency of the RNAi pathway in human cells...
  12. 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
    ..In particular, it has highlighted the assembly and function of the RNA-induced silencing complex (RISC), and has provided guidelines to efficiently silence genes for biological research and therapeutic applications of RNAi...
  13. pmc Methylation as a crucial step in plant microRNA biogenesis
    Bin Yu
    Waksman Institute, Rutgers University, Piscataway, NJ 08854, USA
    Science 307:932-5. 2005
    ..Our studies uncover a new and crucial step in plant miRNA biogenesis and have profound implications in the function of miRNAs...
  14. ncbi microRNA-directed phasing during trans-acting siRNA biogenesis in plants
    Edwards Allen
    Center for Gene Research and Biotechnology, Oregon State University, Corvallis, Oregon 97331, USA
    Cell 121:207-21. 2005
    ....
  15. ncbi A system for stable expression of short interfering RNAs in mammalian cells
    Thijn R Brummelkamp
    Division of Molecular Carcinogenesis, Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands
    Science 296:550-3. 2002
    ..Therefore, the pSUPER vector constitutes a new and powerful system to analyze gene function in a variety of mammalian cell types...
  16. 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
    ..The results suggest a mechanism for the role of the RNAi machinery and small RNAs in targeting of heterochromatin complexes and epigenetic gene silencing at specific chromosomal loci...
  17. pmc Small RNAs in transcriptional gene silencing and genome defence
    Danesh Moazed
    Howard Hughes Medical Institute, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 457:413-20. 2009
    ....
  18. 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...
  19. 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
    ....
  20. ncbi Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes
    Lee Zou
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 300:1542-8. 2003
    ..Our data suggest that RPA-coated ssDNA is the critical structure at sites of DNA damage that recruits the ATR-ATRIP complex and facilitates its recognition of substrates for phosphorylation and the initiation of checkpoint signaling...
  21. pmc Criteria for annotation of plant MicroRNAs
    Blake C Meyers
    Department of Plant and Soil Sciences, Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 19711, USA
    Plant Cell 20:3186-90. 2008
    ..Herein, we update the specific criteria required for the annotation of plant miRNAs, including experimental and computational data, as well as refinements to standard nomenclature...
  22. ncbi Hierarchical action and inhibition of plant Dicer-like proteins in antiviral defense
    Angelique Deleris
    Institut de Biologie Moleculaire des Plantes, CNRS Unité Propre de Recherche UPR 2357, 12, rue du Général Zimmer, 67084 Strasbourg Cedex, France
    Science 313:68-71. 2006
    ..These findings define a molecular framework for studying antiviral silencing and defense in plants...
  23. 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
    ....
  24. ncbi R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway
    Qinghua Liu
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
    Science 301:1921-5. 2003
    The RNA interference (RNAi) pathway is initiated by processing long double-stranded RNA into small interfering RNA (siRNA)...
  25. ncbi Perspective: machines for RNAi
    Yukihide Tomari
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Genes Dev 19:517-29. 2005
    ..Here, we review our current understanding of how small RNAs are produced, how they are loaded into protein complexes, and how they repress gene expression...
  26. pmc Antiviral immunity directed by small RNAs
    Shou Wei Ding
    Department of Plant Pathology and Microbiology, University of California, Riverside, CA 92521, USA
    Cell 130:413-26. 2007
    ..Meanwhile, viral mechanisms to suppress this small RNA-directed immunity by viruses are being elucidated, thereby illuminating an ongoing molecular arms race that likely impacts the evolution of both viral and host genomes...
  27. doi Plant ARGONAUTES
    Herve Vaucheret
    Laboratoire de Biologie Cellulaire, Institut Jean Pierre Bourgin, Institut National de la Recherche Agronomique INRA, 78026 Versailles Cedex, France
    Trends Plant Sci 13:350-8. 2008
    ....
  28. 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
    ..Here, we provide an update on the progress of RNAi therapeutics and highlight novel synthetic materials for the encapsulation and intracellular delivery of nucleic acids...
  29. pmc Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans
    R F Ketting
    The Hubrecht Laboratory and Center for Biomedical Genetics, Uppsalalaan 8, Utrecht, The Netherlands
    Genes Dev 15:2654-9. 2001
    ..dcr-1 mutants show a defect in RNAi. Furthermore, a combination of phenotypic abnormalities and RNA analysis suggests a role for dcr-1 in a regulatory pathway comprised of small temporal RNA (let-7) and its target (e.g., lin-41)...
  30. pmc Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in Arabidopsis
    Junjie Li
    Department of Botany and Plant Sciences, Institute of Integrative Genome Research, University of California, Riverside, Riverside, California 92508, USA
    Curr Biol 15:1501-7. 2005
    ..We conclude that 3'-end methylation is a common step in miRNA and siRNA metabolism and likely protects the 3' ends of the small RNAs from the uridylation activity...
  31. ncbi The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses
    Mitsutoshi Yoneyama
    Department of Tumor Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3 18 22 Honkomagome, Bunkyo ku, Tokyo 113 8613, Japan
    Nat Immunol 5:730-7. 2004
    ..Subsequent gene activation by these factors induced antiviral functions, including type I interferon production. Thus, RIG-I is key in the detection and subsequent eradication of the replicating viral genomes...
  32. 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
    ..The TRBP-Dicer interaction shown raises interesting questions about the potential interplay between RNAi and interferon-PKR pathways...
  33. 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
    ..We further show that the same is true of silencing mediated by small interfering RNA (siRNA) populations. Translational repression is effected in part by the ARGONAUTE proteins AGO1 and AGO10...
  34. ncbi Interfering with disease: a progress report on siRNA-based therapeutics
    Antonin de Fougerolles
    Alnylam Pharmaceuticals Inc, 300 Third Street, Cambridge, Massachusetts 02142, USA
    Nat Rev Drug Discov 6:443-53. 2007
    ..We conclude by reviewing the latest clinical experience with RNAi therapeutics...
  35. ncbi Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer
    Patrick C Ma
    Section of Hematology Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, Chicago, Illinois, USA
    Cancer Res 65:1479-88. 2005
    ..We validated c-Met as potential therapeutic target using small interfering RNA down-regulation of the receptor expression by 50% to 60% in NSCLC cells...
  36. 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
    ..We propose that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germ line...
  37. pmc A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication
    Man Lung Yeung
    Molecular Virology Section, Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892 0460, USA
    J Biol Chem 284:19463-73. 2009
    ..We discuss the similarities and differences between our shRNA findings for HIV-1 using a spreading infection assay in human Jurkat T-cells and results from other investigators who used siRNA-based screenings in HeLa or 293T cells...
  38. ncbi 53BP1, a mediator of the DNA damage checkpoint
    Bin Wang
    Verna and Mars McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 298:1435-8. 2002
    53BP1 binds to the tumor suppressor protein p53 and has a potential role in DNA damage responses. We used small interfering RNA (siRNA) directed against 53BP1 in mammalian cells to demonstrate that 53BP1 is a key transducer of the DNA ..
  39. pmc Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin
    Hideki Yamaguchi
    Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    J Cell Biol 168:441-52. 2005
    ..These results indicate that EGF receptor signaling regulates invadopodium formation through the N-WASP-Arp2/3 pathway and cofilin is necessary for the stabilization and maturation of invadopodia...
  40. doi Specificity of ARGONAUTE7-miR390 interaction and dual functionality in TAS3 trans-acting siRNA formation
    Taiowa A Montgomery
    Molecular and Cellular Biology Program, Oregon State University, Corvallis, OR 97331, USA
    Cell 133:128-41. 2008
    ..miR390 and AGO7, therefore, evolved as a highly specific miRNA guide/effector protein pair to function at two distinct tasiRNA biogenesis steps...
  41. ncbi A two-hit trigger for siRNA biogenesis in plants
    Michael J Axtell
    Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
    Cell 127:565-77. 2006
    ..Therefore, two "hits,"--often, but not always, two cleavage events--constitute a conserved trigger for siRNA biogenesis, a finding with implications for recognition and silencing of aberrant RNA...
  42. ncbi An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster
    Hang Yin
    Department of Cell Biology, Duke University Medical School, Durham, North Carolina 27710, USA
    Nature 450:304-8. 2007
    ..This activating function is probably achieved through interaction with at least 3R-TAS1 piRNA and is essential for germline stem-cell maintenance...
  43. ncbi Nuclear export of microRNA precursors
    Elsebet Lund
    Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706, USA
    Science 303:95-8. 2004
    ..Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps...
  44. pmc MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms
    Yan Zeng
    Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 100:9779-84. 2003
    ..These data suggest that miRNAs and siRNAs can use similar mechanisms to repress mRNA expression and that the choice of mechanism may be largely or entirely determined by the degree of complementary of the RNA target...
  45. doi The impact of target site accessibility on the design of effective siRNAs
    Hakim Tafer
    Institute of Theoretical Biochemistry TBI, University of Vienna, Austria
    Nat Biotechnol 26:578-83. 2008
    ..Overall, RNAxs proves to be a robust siRNA selection tool that substantially improves the prediction of highly efficient siRNAs...
  46. ncbi Asymmetry in the assembly of the RNAi enzyme complex
    Dianne S Schwarz
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, 364 Plantation Street, Worcester, MA 01605, USA
    Cell 115:199-208. 2003
    ..Thus, the common step of RISC assembly is an unexpected source of asymmetry for both siRNA function and miRNA biogenesis...
  47. ncbi Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis
    Xiaoyu Zhang
    Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA
    Cell 126:1189-201. 2006
    ....
  48. ncbi Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi
    Thomas A Volpe
    Cold Spring Harbor Laboratory, Watson School of Biological Sciences, Cold Spring Harbor, NY 11724, USA
    Science 297:1833-7. 2002
    ..We propose that double-stranded RNA arising from centromeric repeats targets formation and maintenance of heterochromatin through RNAi...
  49. ncbi RNA polymerase IV directs silencing of endogenous DNA
    A J Herr
    Sainsbury Laboratory, John Innes Centre, Norwich NR4 7UH, UK
    Science 308:118-20. 2005
    ..The existence of this distinct silencing polymerase may explain the paradoxical involvement of an RNA silencing pathway in maintenance of transcriptional silencing...
  50. pmc Small RNA binding is a common strategy to suppress RNA silencing by several viral suppressors
    Lóránt Lakatos
    Agricultural Biotechnology Center, Plant Biology Institute, Godollo, Hungary
    EMBO J 25:2768-80. 2006
    ..None of the suppressors affected the activity of preassembled RISC complexes. In contrast, each suppressor uniformly inhibited the siRNA-initiated RISC assembly pathway by preventing RNA silencing initiator complex formation...
  51. pmc Slicer function of Drosophila Argonautes and its involvement in RISC formation
    Keita Miyoshi
    Institute for Genome Research, University of Tokushima, Tokushima 770 8503, Japan
    Genes Dev 19:2837-48. 2005
    ..domains of AGO1 and AGO2 demonstrates that other regions in the Argonautes are not strictly necessary for small interfering RNA (siRNA)-binding and cleavage activities...
  52. ncbi RNAi-mediated gene silencing in non-human primates
    Tracy S Zimmermann
    Alnylam Pharmaceuticals Inc, 300 Third Street, Cambridge, Massachusetts 02142, USA
    Nature 441:111-4. 2006
    ..Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs...
  53. ncbi Single processing center models for human Dicer and bacterial RNase III
    Haidi Zhang
    Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland
    Cell 118:57-68. 2004
    ..Based on these and other data, we propose that Dicer functions through intramolecular dimerization of its two RNase III domains, assisted by the flanking RNA binding domains, PAZ and dsRBD...
  54. ncbi Control of translation and mRNA degradation by miRNAs and siRNAs
    Marco Antonio Valencia-Sanchez
    Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, University of Arizona, Tucson, Arizona 85721, USA
    Genes Dev 20:515-24. 2006
    ..An emerging theme is that miRNAs, and siRNAs to some extent, target mRNAs to the general eukaryotic machinery for mRNA degradation and translation control...
  55. ncbi The RNAi revolution
    Carl D Novina
    Nature 430:161-4. 2004
  56. ncbi A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen
    Jason Moffat
    Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA
    Cell 124:1283-98. 2006
    ..This work provides a widely applicable resource for loss-of-function screens, as well as a roadmap for its application to biological discovery...
  57. pmc Common functions for diverse small RNAs of land plants
    Michael J Axtell
    Department of Biology and Huck Institutes of the Life Sciences, Pensylvania State University, University Park, PA 16802, USA
    Plant Cell 19:1750-69. 2007
    ..Diverse, lineage-specific, small RNAs can therefore perform common biological functions in plants...
  58. 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
    ..Thus, assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy...
  59. 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...
  60. ncbi Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration
    Takashi Watanabe
    Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi 466 8550, Japan
    Dev Cell 7:871-83. 2004
    ....
  61. 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 mammals...
  62. pmc Novel and stress-regulated microRNAs and other small RNAs from Arabidopsis
    Ramanjulu Sunkar
    Institute for Integrative Genome Biology and Department of Botany and Plant Sciences, University of California, Riverside, California 92521, USA
    Plant Cell 16:2001-19. 2004
    ....
  63. pmc Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans
    R Lu
    Institute for Integrative Genome Biology and Department of Plant Pathology, University of California, Riverside, California 92521, USA
    Nature 436:1040-3. 2005
    ..This work establishes a C. elegans model for genetic studies of animal virus-host interactions and indicates that mammals might use a siRNA pathway as an antiviral response...
  64. pmc Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies
    Chengjian Li
    Department of Biochemistry and Molecular Pharmacology and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, 01605, USA
    Cell 137:509-21. 2009
    ..Transposons targeted by this second pathway often reside in the flamenco locus, which is expressed in somatic ovarian follicle cells, suggesting a role for piRNAs beyond the germline...
  65. pmc Brk activates rac1 and promotes cell migration and invasion by phosphorylating paxillin
    Hsin Yi Chen
    Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
    Mol Cell Biol 24:10558-72. 2004
    ..Together, our findings identify novel signaling and biological roles of Brk and indicate the first potential link between Brk and metastatic malignancy...
  66. pmc Nuclear processing and export of microRNAs in Arabidopsis
    Mee Yeon Park
    Department of Biology, University of Pennsylvania, Philadelphia, PA 19104 6018, USA
    Proc Natl Acad Sci U S A 102:3691-6. 2005
    ..These results demonstrate that HST and PSD do not share RNA cargos in nuclear export and strongly suggest that there are multiple nuclear export pathways for these small RNAs in Arabidopsis...
  67. pmc Arabidopsis lyrata small RNAs: transient MIRNA and small interfering RNA loci within the Arabidopsis genus
    Zhaorong Ma
    Integrative Biosciences PhD Program in Bioinformatics and Genomics, Huck Institutes of the Life Sciences, Pensylvania State University, University Park, Pensylvania 16802, USA
    Plant Cell 22:1090-103. 2010
    ..thaliana. Altogether, our findings indicate that many MIRNAs and most p4-siRNA hot spots are rapidly changing and evolutionarily transient within the Arabidopsis genus...
  68. ncbi Expression profiling reveals off-target gene regulation by RNAi
    Aimee L Jackson
    Rosetta Inpharmatics LLC, 12040 115th Avenue NE, Kirkland, Washington 98034, USA
    Nat Biotechnol 21:635-7. 2003
    RNA interference is thought to require near-identity between the small interfering RNA (siRNA) and its cognate mRNA...
  69. ncbi Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma
    Siwen Hu-Lieskovan
    Department of Pathology, Children s Hospital Los Angeles, Los Angeles, California 90027, USA
    Cancer Res 65:8984-92. 2005
    ..We show here that the systemic delivery of sequence-specific small interfering RNA (siRNA) against the EWS-FLI1 gene product by a targeted, nonviral delivery system dramatically inhibits ..
  70. ncbi Identification of novel argonaute-associated proteins
    Gunter Meister
    Laboratory of RNA Molecular Biology, The Rockefeller University, 1230 York Avenue, Box 186, New York, New York 10021, USA
    Curr Biol 15:2149-55. 2005
    ..The new proteins localize, similar to Ago proteins, to mRNA-degrading cytoplasmic P bodies, and they are functionally required to mediate miRNA-guided mRNA cleavage...
  71. doi Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes
    Toshiaki Watanabe
    Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima 411 8540, Japan
    Nature 453:539-43. 2008
    ..Our results reveal a role for endogenous siRNAs in mammalian oocytes and show that organisms lacking RdRP activity can produce functional endogenous siRNAs from naturally occurring dsRNAs...
  72. ncbi Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells
    Daniel H Kim
    Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, 1450 E Duarte Road, Duarte, California 91010, USA
    Nat Struct Mol Biol 13:793-7. 2006
    ..These results establish a connection between RNAi components AGO1 and TRBP2, RNAPII transcription and Polycomb-regulated control of gene expression...
  73. pmc Profiling essential genes in human mammary cells by multiplex RNAi screening
    Jose M Silva
    Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Science 319:617-20. 2008
    ..These studies establish a practical platform for genome-scale screening of complex phenotypes in mammalian cells and demonstrate that RNAi can be used to expose genotype-specific sensitivities...
  74. 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
    ....
  75. pmc The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells
    Fanni Gergely
    Department of Pharmacology, University of Cambridge, Wellcome Trust Cancer Research UK Institute, Cambridge CB2 1QR, UK
    Genes Dev 17:336-41. 2003
    ..Thus, in human somatic cells, ch-TOG appears to play a major role in organizing spindle poles, and a more minor role in stabilizing spindle microtubules that is, at least in part, mediated via an interaction with TACC3...
  76. pmc Probing the microRNA and small interfering RNA pathways with virus-encoded suppressors of RNA silencing
    Patrice Dunoyer
    Institut de Biologie Moléculaire des Plantes du Centre National de la Recherche Scientifique, 67084 Strasbourg Cedex, France
    Plant Cell 16:1235-50. 2004
    ..Therefore, silencing suppressors are valuable probes of the complexity of RNA silencing...
  77. ncbi Cofilin promotes actin polymerization and defines the direction of cell motility
    Mousumi Ghosh
    Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Science 304:743-6. 2004
    ..We propose a role for cofilin that is distinct from its role as an actin-depolymerizing factor...
  78. 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
    ..For siRNAs, virtually all RISC is assembled through this cleavage-assisted mechanism. In contrast, passenger-strand cleavage is not important for the incorporation of miRNAs that derive from mismatched duplexes...
  79. pmc A pathogen-inducible endogenous siRNA in plant immunity
    Surekha Katiyar-Agarwal
    Department of Plant Pathology, Center for Plant Cell Biology and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA
    Proc Natl Acad Sci U S A 103:18002-7. 2006
    ..This siRNA contributes to RPS2-mediated race-specific disease resistance by repressing PPRL, a putative negative regulator of the RPS2 resistance pathway...
  80. pmc Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints
    Hui Zhao
    Department of Cell Biology and Physiology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8228, 660 South Euclid Avenue, St Louis, MO 63110 1093, USA
    Proc Natl Acad Sci U S A 99:14795-800. 2002
    ..These findings indicate that Chk1 directly phosphorylates Cdc25A during an unperturbed cell cycle, and that phosphorylation of Cdc25A by Chk1 is required for cells to delay cell cycle progression in response to double-strand DNA breaks...
  81. pmc RNA interference: biology, mechanism, and applications
    Neema Agrawal
    International Center for Genetic Engineering and Biotechnology, New Delhi 110 067, India
    Microbiol Mol Biol Rev 67:657-85. 2003
    ..Because of its exquisite specificity and efficiency, RNAi is being considered as an important tool not only for functional genomics, but also for gene-specific therapeutic activities that target the mRNAs of disease-related genes...
  82. ncbi Deregulated Akt3 activity promotes development of malignant melanoma
    Jill M Stahl
    Department of Pharmacology, The Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033, USA
    Cancer Res 64:7002-10. 2004
    ..The predominant Akt isoform active in melanomas was identified by showing that small interfering RNA (siRNA) against only Akt3, and not Akt1 or Akt2, lowered the amount of phosphorylated (active) Akt in ..
  83. ncbi siRNA and isRNA: two edges of one sword
    Martin Schlee
    Division of Clinical Pharmacology, Department of Medicine, University of Bonn, Sigmund Freud Strasse 25, 53127 Bonn, Germany
    Mol Ther 14:463-70. 2006
    ....
  84. pmc Genome-wide association of histone H3 lysine nine methylation with CHG DNA methylation in Arabidopsis thaliana
    Yana V Bernatavichute
    Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 3:e3156. 2008
    ..These results suggest a complex interplay between H3K9m2 and different types of DNA methylation and suggest that distinct mechanisms control H3K9m2 in different compartments of the genome...
  85. pmc qiRNA is a new type of small interfering RNA induced by DNA damage
    Heng Chi Lee
    Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
    Nature 459:274-7. 2009
    ..Furthermore, the Neurospora RNA interference mutants show increased sensitivity to DNA damage, suggesting a role for qiRNAs in the DNA-damage response by inhibiting protein translation...
  86. pmc A core function for p120-catenin in cadherin turnover
    Michael A Davis
    Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232 6840, USA
    J Cell Biol 163:525-34. 2003
    ..The data reveal a core function of p120 in cadherin complexes, and strongly predict a dose-dependent loss of E-cadherin in tumors that partially or completely down-regulate p120...
  87. ncbi Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA
    Kin Hang Kok
    Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China
    J Biol Chem 282:17649-57. 2007
    ..TRBP and PACT form a triple complex with Dicer and facilitate the production of small interfering RNA (siRNA) by Dicer...
  88. pmc Artificial microRNAs as siRNA shuttles: improved safety as compared to shRNAs in vitro and in vivo
    Ryan L Boudreau
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52240, USA
    Mol Ther 17:169-75. 2009
    ..These findings, together with data from earlier work in mouse striata, suggest that miRNA-based platforms are better suited for therapeutic silencing in the mammalian brain...
  89. pmc Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage
    Randi G Syljuåsen
    Institute of Cancer Biology, Department of Cell Cycle and Cancer, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark
    Mol Cell Biol 25:3553-62. 2005
    ..Here, we show that Chk1 inhibition by two distinct drugs, UCN-01 and CEP-3891, or by Chk1 small interfering RNA (siRNA) leads to phosphorylation of ATR targets...
  90. ncbi Cep97 and CP110 suppress a cilia assembly program
    Alexander Spektor
    Department of Pathology and NYU Cancer Institute, New York University School of Medicine, Smilow Research Center, 522 First Avenue, New York, NY 10016, USA
    Cell 130:678-90. 2007
    ..Identification of Cep97 and other genes involved in regulation of cilia assembly may accelerate our understanding of human ciliary diseases, including renal disease and retinal degeneration...
  91. ncbi Disabled-2 small interfering RNA modulates cellular adhesive function and MAPK activity during megakaryocytic differentiation of K562 cells
    Ching Ping Tseng
    Graduate Institute of Medical Biotechnology Chang Gung University, Kweishan, Taoyuan, Taiwan
    FEBS Lett 541:21-7. 2003
    ..To delineate the consequences of DAB2 induction, a DNA vector-based small interfering RNA (siRNA) was designed to intervene in DAB2 expression...
  92. ncbi Human IRGM induces autophagy to eliminate intracellular mycobacteria
    Sudha B Singh
    Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
    Science 313:1438-41. 2006
    ..We also identified a function for a human IRG protein in the control of intracellular pathogens and report that the human Irgm1 ortholog, IRGM, plays a role in autophagy and in the reduction of intracellular bacillary load...
  93. ncbi Construction of small RNA cDNA libraries for deep sequencing
    Cheng Lu
    Department of Plant and Soil Sciences, Delaware Biotechnology Institute, University of Delaware, Newark, DE 19711, USA
    Methods 43:110-7. 2007
    ..Here, we describe the methods used in our laboratory to construct small RNA cDNA libraries for high-throughput sequencing using technologies such as MPSS, 454 or SBS...
  94. pmc Proton-sponge coated quantum dots for siRNA delivery and intracellular imaging
    Maksym V Yezhelyev
    Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA
    J Am Chem Soc 130:9006-12. 2008
    ..These new insights and capabilities represent a major step toward nanoparticle engineering for imaging and therapeutic applications...
  95. pmc A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity
    Jesper B Bramsen
    Department of Molecular Biology, University of Aarhus, Arhus, Nucleic Acid Center, University of Southern Denmark, Odense, Denmark
    Nucleic Acids Res 37:2867-81. 2009
    ..Collectively, our results provide unique insights into the tolerance for chemical modifications and provide a simple guide to successful chemical modification of siRNAs with improved activity, stability and low toxicity...
  96. pmc Allele-specific silencing of dominant disease genes
    Victor M Miller
    Department of Neurology, Graduate Program in Genetics, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 100:7195-200. 2003
    b>Small interfering RNA (siRNA) holds therapeutic promise for silencing dominantly acting disease genes, particularly if mutant alleles can be targeted selectively...
  97. ncbi Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo
    Adam D Judge
    Protiva Biotherapeutics, 100 3480 Gilmore Way, Burnaby, BC, Canada V5G 4Y1
    Mol Ther 13:494-505. 2006
    ..This approach to siRNA design and delivery should prove widely applicable and represents an important step in advancing synthetic siRNA into a broad range of therapeutic areas...
  98. pmc Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad
    Kazumichi M Nishida
    Institute for Genome Research, University of Tokushima, Tokushima, Japan
    RNA 13:1911-22. 2007
    ..These results provide the first biochemical insights into gene silencing mechanisms mediated by Aub and piRNAs in fly testes...
  99. ncbi Induction and suppression of RNA silencing by an animal virus
    Hongwei Li
    Department of Plant Pathology and Center for Plant Cell Biology, University of California, Riverside, CA 92521, USA
    Science 296:1319-21. 2002
    ..These findings establish RNA silencing as an adaptive antiviral defense in animal cells. B2 also inhibits RNA silencing in transgenic plants, providing evidence for a conserved RNA silencing pathway in the plant and animal kingdoms...
  100. 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
    ..Thus, our evidence supports a model in which Argonaute contributes "Slicer" activity to RISC, providing the catalytic engine for RNAi...
  101. pmc Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
    James Brugarolas
    Dana Farber Cancer Institute and Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Genes Dev 18:2893-904. 2004
    ..Inhibition of mTOR function by hypoxia is likely to be important for tumor suppression as TSC2-deficient cells maintain abnormally high levels of cell proliferation under hypoxia...

Research Grants74

  1. TIMOTHY L SITA; Fiscal Year: 2016
    ..We will utilize small interfering RNA (siRNA) duplexes densely conjugated to the surface of gold nanoparticles (MGMTi-Spherical Nucleic Acids (..
  2. Novel genomic effects of Y-linked polymorphisms
    Daniel L Hartl; Fiscal Year: 2012
    ..by regulatory pathways associated with position-effect variegation (PEV) and/or repeat- associated small interfering RNA (rasiRNA)...
  3. Margot S Damaser; Fiscal Year: 2014
    ..an infusion of MSCs in which homing cytokine receptors have been knocked down via transfection with small interfering RNA (siRNA)...
  4. Role of estrogen-related receptors in cardiac and skeletal muscle
    Janice M Huss; Fiscal Year: 2010
    ..Our findings will elucidate the potential for ERRs as therapeutic targets for widespread human diseases associated with metabolic dysregulation. ..
  5. Hepatocarcinogenesis Secondary to Hepatitis C
    Srikanta Dash; Fiscal Year: 2012
    ..iii). Recently, we have reported that small interfering RNA (siRNA) targeted to the IRES region that can inhibit translation of six different HCV genotypes...
  6. Reactivation of Fetal Gamma-globin Genes for the Treatment of Beta-globin Disorde
    Osamu Tanabe; Fiscal Year: 2010
    ..The first will be to develop highly efficient small interfering RNA (siRNA) duplexes that specifically knock-down TR2, TR4, or their potential co-regulatory proteins by RNA ..
  7. Zhenfeng Duan; Fiscal Year: 2014
    ..novel class of biocompatible dextran-based polymeric nano-assembled structures for encapsulation and delivery of small interfering RNA that can silence specific genes in resistant cells. and cytotoxic drugs for maximum cell-kill effect.
  8. Robert W McCarley; Fiscal Year: 2016
    ..Following our successful use of small interfering RNA (siRNA) in the brainstem, the same technique will be used to knockdown orexin receptors in the BF and ..
  9. A Novel Epigenetic Gene Silencing Technology
    MING MING contact ZHOU; Fiscal Year: 2010
    ..RNA interference (RNAi) that blocks gene translation to protein by small interfering RNA (siRNA)-triggered messenger RNA destruction has had transformative impact in research and also generated ..
  10. The new biology of estrogen action in aromatase resistance breast cancer cells
    JOAN SUEDEE LEWIS-WAMBI; Fiscal Year: 2011
    ..reaction (PCR) to measure changes in mRNA levels, confocal microscopy to study protein translocalization, small interfering RNA (siRNA) and transfection analyses to suppress gene expression, cell invasion and migration assay to ..
  11. Hepatic expression of small hairpin RNA using gutless adenoviral vectors
    Nuria Morral; Fiscal Year: 2012
    ..The small interfering RNA (siRNA) technology has become the tool of choice to study gene function and validate targets because it ..
  12. CHARACTERIZATION OF NOVEL BUTADIENE-INDUCED PUTATIVE p53 TARGET GENES
    Perpetua M Muganda; Fiscal Year: 2010
    ..This project will utilize high-throughput approaches involving small interfering RNA, chromatin immunoprecipitation-quantitative PCR assays, reporter gene assays, polymerase chain reaction ..
  13. JOHN VINCENT BRIGANDE; Fiscal Year: 2014
    ..In Aim 2, we propose to transfect otic precursors with expression plasmid or small interfering RNA (siRNA) by transuterine microinjection of surface remodeled protein/nucleic acid complexes...
  14. Development of a radioligand for assay of angiotensin-converting enzyme-2(ACE-2)
    ROBERT CHARLES SPETH; Fiscal Year: 2013
    ..or deletion of ACE-2 in transgenic mice or rats virally transfected with ACE-2 mRNA or with a small interfering RNA that inhibits ACE-2 synthesis...
  15. Understanding and Eliminating Oncogenic EGFR Signaling in Malignant Glioma
    Alain Charest; Fiscal Year: 2013
    ..toxicity profiles and efficacy spectrum of various nanotechnology platforms for the efficient delivery of small interfering RNA (siRNA) molecules to GBM tumor cells in vivo...
  16. siRNA Therapy and Imaging Assessment in Ischemic Stroke
    Marytheresa Ifediba; Fiscal Year: 2012
    ..selected RNA interference technology, a highly- selective and potent gene silencing technique that employs small interfering RNA (siRNA) molecules...
  17. Functional analysis of AMD-associated HTRA1 promoter polymorphism
    Noriko Esumi; Fiscal Year: 2010
    ..Cotransfection with an expression vector and small interfering RNA (siRNA) transfection will be used for gain-of-function analysis by overexpression and loss-of-function ..
  18. Elimination of Carcinogen-Induced Tumor Stem Cells by ATF5 Loss of Function.
    JAMES ANGELASTRO; Fiscal Year: 2009
    ..of functional ATF5, achieved through overexpression of its dominant negative or loss of ATF5 expression by small interfering RNA, accelerates neuronal and glial differentiation. High expression of ATF5 occurs in glioblastoma tumors...
  19. ESTROGEN AND COGNITION OVER THE LIFESPAN
    Thomas C Foster; Fiscal Year: 2010
    ..Specific aim 3 will employ viral vector mediated delivery of small interfering RNA for the down regulation of target genes, ERalpha or ERbeta, and will test the hypothesis that decreased ..
  20. The functional role of DRH-1 in RNAi directed viral immunity
    Rui Lu; Fiscal Year: 2013
    ..with the processing of viral replication intermediates (in the form of double stranded RNA (dsRNA)), into small interfering RNA (siRNA) duplexes by RNase III enzymes...
  21. A new synergy for flavivirus therapy: RNAi enhancement and viral mutagens
    KATHRYN ALYCE HANLEY; Fiscal Year: 2012
    ..RNA interference is a ubiquitious antiviral defense of eukaryotes that acts by targeting small interfering RNA's (siRNA's) to complementary regions in the viral genome;genomes bound to siRNA's are ..
  22. QD-BRET nanosensors for protease detection and imaging
    Jianghong Rao; Fiscal Year: 2012
    ..in xenografted tumors in a mouse model;3) to image the inhibition efficacy of uPA, MMP-2 and MMP-7 by small interfering RNA and to probe the cross-activation relationship among the three proteases...
  23. Mark D Zabel; Fiscal Year: 2016
    ..We have recently developed a novel small interfering RNA (siRNA) delivery system using liposome-siRNA-peptide complexes (LSPCs) to protect siRNAs from serum ..
  24. Lipidoid Nanoparticles with Simultaneous Multi-Gene Regulation for Cancer Therapy
    Yizhou Dong; Fiscal Year: 2013
    ..Gene therapy, the use of DNA as a pharmaceutical agent is specific to the up-regulation of one gene, while small interfering RNA (siRNA) is specific down-regulating one gene...
  25. Le Shen; Fiscal Year: 2016
    ..refute this view and show that decreased expression of the tight junction protein, occludin, either by small interfering RNA mediated knockdown in cultured intestinal epithelial cells or by gene knockout in mice, decreases TNF-..
  26. FUNCTION AND REGULATION OF GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 2
    MARIA R GONZALEZ BARO; Fiscal Year: 2012
    ....
  27. Mechanism of H. pylori-induced risk reduction for inflammatory bowel disease
    Jay Luther; Fiscal Year: 2009
    ..Briefly, by using H. pylori genomic DNA and TLR9 knockout mice and small interfering RNA to knockdown TLR-9, we will examine the role of bacterial DNA-TLR-9 interaction in shaping the phenotype ..
  28. Flordeliza S Villanueva; Fiscal Year: 2015
    ..Although RNAi, and specifically small interfering RNA (siRNA), has shown much promise for the treatment of cancer and a broad spectrum of other diseases, ..
  29. MOLECULAR AND CELLULAR ANALYSIS OF G PROTEIN FUNCTION
    Catherine H Berlot; Fiscal Year: 2013
    ..Silencing the G protein [unreadable]1 subunit using small interfering RNA (siRNA) or inhibition of [unreadable]? signaling with the small molecule, 1 gallein, leads to increased T ..
  30. Nicholas C Brecha; Fiscal Year: 2014
    ..Specific aim 3 will test the hypothesis that Ca2+ channel antagonists and small interfering RNA (siRNA) antisense Ca2+ channel subunit vectors regulate Ca2+ signaling, and enhance ganglion cell survival ..
  31. Microvascular Endothelial Cells in the Pathogenesis of Chronic Kidney Injury
    Ikuyo Yamaguchi; Fiscal Year: 2011
    ..UUO studies will use VE-cadherin heterozygote () mice and small interfering RNA (siRNA) to investigate how the level of VE-cadherin expression affects the progression of chronic renal ..
  32. RNA Interference for the Treatment of Ebola and Marburg Hemorrhagic Fever
    Ian MacLachlan; Fiscal Year: 2013
    ..postexposure protection of nonhuman primates against a lethal ZEBOV challenge using a combination of small interfering RNA (siRNA) targeting the ZEBOV L polymerase, viral protein (VP) 24, and VP35 formulated in stable nucleic ..
  33. Lina M Obeid; Fiscal Year: 2016
    ..This will be done by blocking ceramidase activity in cells and in vivo using small interfering RNA to the different ceramidases...
  34. PARP-1 is a Negative Modulator of the Heart Shock Response
    RAJESH K ANEJA; Fiscal Year: 2010
    ..Thus, in Aim 1,1 will confirm the data obtained in PARP-/- cells by studying wt cells transfected with small interfering RNA (siRNA) directed against PARP-1...
  35. Quantitative stepwise analysis of RNA interference
    Sua Myong; Fiscal Year: 2012
    ..Despite the differences in their origin, both small interfering RNA (siRNA) and micro RNA (miRNA) are processed by the same protein machineries of the RNAi pathway in human...
  36. Intracellular Target of Sphingosine-1-Phosphate
    GRAHAM M STRUB; Fiscal Year: 2010
    ..This will be accomplished by downregulation of expression of each of the kinases with small interfering RNA, and observing the effects on transcription factor activity and gene expression...
  37. Quantitative Trait Genes for Circadian Phenotypes
    John R Hofstetter; Fiscal Year: 2013
    ..Add a small interfering RNA (siRNA) corresponding to the complimentary strand of the candidate-gene's transcript to the culture&..
  38. GD3S knockdown to improve cognitive and motor deficits in models of parkinsonism
    Michael P McDonald; Fiscal Year: 2013
    ..The effects of GD3S inhibition are to reduce aggregates of proteins such as 1-synuclein, reduce oxidative stress, prevent neurodegeneration, and improve motor and cognitive function. ..
  39. GANESAN LENIN KAMATCHI; Fiscal Year: 2015
    ..In this regard, we will use small interfering RNA (siRNA) to silence the selected Cav subunits...
  40. Targeted delivery of TGFbeta blockade to diseased glomeruli
    Yufeng Huang; Fiscal Year: 2010
    ..By combining small interfering RNA (siRNA) with nanoparticle technology, we have recently developed a mesangial cell-specific, ligand-..
  41. Zaijie Jim Wang; Fiscal Year: 2016
    ..of chronic pain in SCD, we will conduct pharmacological studies to inhibit CaMKIIa using chemical, small interfering RNA (siRNA), and gene knockout methods...
  42. ENGINEERED GLUCOSE METABOLISM IN INSULIN SECRETING CELLS
    Christopher B Newgard; Fiscal Year: 2010
    ..b>Small interfering RNA (siRNA) technology will be used to modulate expression of key enzymes and mediators of metabolic function ..
  43. Nipah &Hendra Virus Nonhuman Primate Model &Therapeutics Development
    THOMAS WILLIAM GEISBERT; Fiscal Year: 2013
    ..4. Determine the passive protective efficacy of fusion inhibitor peptide and small interfering RNA (siRNA) therapy for Nipah and Hendra virus infection in the AGM...
  44. RICHARD ALAN JOHNSTON; Fiscal Year: 2014
    ..inflammation, from MH-S cells, an immortalized alveolar macrophage cell line in the presence or absence of small interfering RNA directed against murine ChemR23...
  45. Method Development for a Next Generation Miniaturized Genomic Screening Platform
    Peter Kahn; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Every gene has its own set of small RNA molecules, known as small interfering RNA (siRNA), that inhibit expression of the gene's proteins...
  46. Biological and Therapeutic Significance of TG2 in Pancreatic Cancer
    Kapil Mehta; Fiscal Year: 2010
    ..promotes constitutive activation of the focal adhesion kinase (FAK), Akt and NF-:B;c) inhibition of TG2 by small interfering RNA (siRNA) inhibited invasion and induced autophagic death in pancreatic cancer cells;conversely, d) ectopic ..
  47. Jun Ming Zhang; Fiscal Year: 2016
    ..been largely ignored as a therapeutic target;however, knocking down this channel in the DRG in vivo with small interfering RNA can completely block development of pain behaviors induced by local DRG inflammation, without affecting ..
  48. Multichannel Electrosonic Actuation Microarray for Cell-Based Screening
    JOHN MARK MEACHAM; Fiscal Year: 2010
    ..to greatly accelerate discovery of cancer therapies by enabling simultaneous screening of synthetic small interfering RNA (siRNA) for different effects on cell function...
  49. MULTI-TARGETED RNAI THERAPEUTICS FOR GLIOBLASTOMA MULTIFORME (GBM)
    Patrick Y Lu; Fiscal Year: 2010
    ..Three small interfering RNA (siRNA) cocktails targeting EGFR-VEGF-AGT, or EGFR-VEGF-MMP9, or EGFR-VEGF-TGF respectively, will be ..
  50. Dineo Khabele; Fiscal Year: 2014
    ..The candidate has recently published that HDAC inhibition with class I selective HDACi and small interfering RNA (siRNA) gene silencing of class I HDACs, particularly HDAC3 suppress cell proliferation in ovarian cancer ..
  51. Targeted Liposomal Delivery of CD147 siRNA to Murine Head and Neck Cancer Models
    Nadarajah Vigneswaran; Fiscal Year: 2010
    ..of this proposal is to silence CD147 in murine Head and Neck Squamous Cell Carcinomas (HNSCC) models using small interfering RNA (siRNA) with the aim of reversing their chemoresistance and metastatic potential...
  52. Tumor-targeted silencing of Bcl-2/Bcl-xL by the self-assembled siRNA-nanovectors
    Liang Xu; Fiscal Year: 2010
    ..The potent, sequence-specific gene silencing by small interfering RNA (siRNA) has become a powerful tool in cancer research and holds significant potential as novel molecular ..
  53. Target migratory nature of glioblastoma stem cells
    Cho Lea Tso; Fiscal Year: 2010
    ..Our research goal is to identify genes that regulate GSC migration via a small interfering RNA (siRNA) screening approach...
  54. Fan Yuan; Fiscal Year: 2016
    ..endocytic pathways will be selectively blocked by pharmaceutical inhibitors, dominant-negative mutants, or small interfering RNA (siRNA) that can knock down expression of specific genes in endocytic pathways...
  55. Chung Owyang; Fiscal Year: 2015
    ..imaging studies, single cel RT-PCR, and signal transduction studies using pharmacological tools and small interfering RNA technology...
  56. Illuminating the Mechanistic Pathways of Polymer-Mediated Nucleic Acid Delivery
    Theresa M Reineke; Fiscal Year: 2010
    ..mechanisms and kinetics with three polynucleotide forms: plasmid DNA, oligodeoxynucleotide decoys, and small interfering RNA, in two cell types, H9C2(2-1) and Hela cells...
  57. Tolerance to TLR Ligands in the Intestinal Epithelium
    Anatoly V Grishin; Fiscal Year: 2010
    ..epithelium by determining responses to different TLR ligands in enterocytes following forced expression or small interfering RNA (siRNA) silencing of A20. 2. Determine the role of CYLD in enterocyte tolerance to Fla...
  58. Ping Zhou; Fiscal Year: 2016
    ..Viral gene transfer and small interfering RNA (siRNA) will be used to increase or decrease PHB expression in neuronal cultures or in the mouse ..
  59. NASSER HUSSEIN ZAWIA; Fiscal Year: 2014
    ..Studies from our lab have provided convincing evidence that either silencing of the Sp1 gene using small interfering RNA (Basha et al...
  60. HIV-1 TAR derived miRNA: Implications for Latency and Pathogenesis
    Fatah Kashanchi; Fiscal Year: 2010
    ..The RNAi pathway generates small interfering RNA (siRNA) or micro RNA (miRNA) from either long double stranded stretches of RNA or RNA hairpins, ..
  61. Calcium entry pathway in hypoxic pulmonary hypertension
    Jian Wang; Fiscal Year: 2010
    ..As initial tests of these hypotheses, we will determine: 1) if treatment of PASMCs with small interfering RNA (siRNA) specific for TRPC proteins blocks increases in [Ca2+]i and CCE caused by acute hypoxia;2) the ..
  62. STRUCTURE AND FUNCTION OF NUCLEIC ACID THERAPEUTICS
    Martin Egli; Fiscal Year: 2012
    ..to optimize their structure and activity for future applications as antisense oligonucleotide (AON) and small interfering RNA (siRNA) therapeutics, to devise an etiology of nucleic acid structure, and to determine the origins of ..
  63. HK polymers as transfection reagents for siRNA delivery
    Frank Xie; Fiscal Year: 2005
    ..cells, the phenomenon can be invoked by introducing small 19-21 nucleotide long RNA duplexes, known as small interfering RNA (siRNA) into cells...
  64. Transcriptional Regulation of Matrix Metalloproteinase-3 (MMP-3)
    RUTH BORGHAEI; Fiscal Year: 2007
    ..Our increased understanding of these transcriptional control mechanisms, and how they sometimes fail, will be important to improve our understanding of a variety of pathologies. [unreadable] [unreadable] [unreadable]..
  65. Orexins in Rapid Eye Movement Sleep Control.
    Mahesh Thakkar; Fiscal Year: 2009
    ..We will use novel combinations of multi- disciplinary methods including the in vivo use of small interfering RNA (siRNA) for knockdowns of orexin type II receptor in the pontis oralis/ventral subcoeruleus region (PNO) ..
  66. Role of PPAR-gamma Isoforms in Regulation of Macrophage apoE & LPL Expression
    Jheem Medh; Fiscal Year: 2006
    ..For reducing the expression of proteins, small interfering RNA (siRNA) complementary to specific PPAR-g isoforms will be used to destroy PPAR-g isoform-specific ..
  67. Inhibition of Collagen Synthesis by RNA Interference
    Kyonggeun Yoon; Fiscal Year: 2003
    ..With the recent discovery of small interfering RNA (siRNA), various forms of small dsRNA are now emerging as a novel class of therapeutics, which cause ..
  68. Effect of Versican Mutation on Limb Development In Vitro
    ANTHONY CAPEHART; Fiscal Year: 2006
    ..knock down of versican expression in ovo will be performed by microinjection of adenovirally encoded small interfering RNA constructs into limb mesenchyme...
  69. New approaches to studying host-chlamydia interactions
    Joanne Engel; Fiscal Year: 2006
    ..Drosophila readily takes up small interfering RNA, allowing efficient inactivation of genes in whole flies as well as in Drosophila tissue culture cells...
  70. The Role of Polycystins in the Regulation of Intracellular Calcium and Vascular R
    Qi Qian; Fiscal Year: 2007
    ..mutant gene, and TRPC1 - the protein product of trpc1 gene that is a SOC subunit) and gene silencing using small interfering RNA (siRNA), intracellular Ca2+ imaging, and patch clamp techniques including perforated whole-cell and cell-..
  71. HUMAN DNA REPAIR ENZYMES FOR REDOX AND ALKYLATION DAMAGE
    BRUCE F DEMPLE; Fiscal Year: 2010
    ..Directly test the role of SirtG in DNA repair and the sub-pathways of BER. ..
  72. Nicotinic receptor-mediated action of tobacco nitrosamines on respiratory cells
    SERGEI GRANDO; Fiscal Year: 2007
    ..We will identify the nAChR- selective drug, small interfering RNA, or antisense oligonucleotides, that can abolish tumor-inducing activities of test nitrosamines...