rna splicing

Summary

Summary: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.

Top Publications

  1. ncbi The spliceosome: design principles of a dynamic RNP machine
    Markus C Wahl
    Makromolekulare Röntgenkristallographie, Max Planck Institut fur biophysikalische Chemie, Am Fassberg 11, D 37077 Gottingen, Germany
    Cell 136:701-18. 2009
  2. ncbi Mapping and quantifying mammalian transcriptomes by RNA-Seq
    Ali Mortazavi
    Division of Biology, MC 156 29, California Institute of Technology, Pasadena, California 91125, USA
    Nat Methods 5:621-8. 2008
  3. ncbi XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    H Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Cell 107:881-91. 2001
  4. pmc RNA and disease
    Thomas A Cooper
    Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
    Cell 136:777-93. 2009
  5. ncbi IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA
    Marcella Calfon
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Nature 415:92-6. 2002
  6. ncbi Listening to silence and understanding nonsense: exonic mutations that affect splicing
    Luca Cartegni
    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 3:285-98. 2002
  7. ncbi The transcriptional landscape of the mammalian genome
    P Carninci
    Science 309:1559-63. 2005
  8. ncbi Improved splice site detection in Genie
    M G Reese
    Human Genome Informatics Group, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    J Comput Biol 4:311-23. 1997
  9. ncbi Identification and characterization of a spinal muscular atrophy-determining gene
    S Lefebvre
    Unite de Recherches sur les Handicaps Genetiques de l Enfant, Institut National de la Sante et de la Recherche Medicale, Institut Necker, Hopital des Enfants Malades, Paris, France
    Cell 80:155-65. 1995
  10. ncbi The SR protein family of splicing factors: master regulators of gene expression
    Jennifer C Long
    Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH42XU, UK
    Biochem J 417:15-27. 2009

Detail Information

Publications377 found, 100 shown here

  1. ncbi The spliceosome: design principles of a dynamic RNP machine
    Markus C Wahl
    Makromolekulare Röntgenkristallographie, Max Planck Institut fur biophysikalische Chemie, Am Fassberg 11, D 37077 Gottingen, Germany
    Cell 136:701-18. 2009
    ....
  2. ncbi Mapping and quantifying mammalian transcriptomes by RNA-Seq
    Ali Mortazavi
    Division of Biology, MC 156 29, California Institute of Technology, Pasadena, California 91125, USA
    Nat Methods 5:621-8. 2008
    ..We observed 1.45 x 10(5) distinct splices, and alternative splices were prominent, with 3,500 different genes expressing one or more alternate internal splices...
  3. ncbi XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    H Yoshida
    Graduate School of Biostudies, Kyoto University, Kyoto 606 8304, Japan
    Cell 107:881-91. 2001
    ..Our results reveal features of the UPR conserved during evolution and clarify the relationship between IRE1- and ATF6-dependent pathways...
  4. pmc RNA and disease
    Thomas A Cooper
    Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
    Cell 136:777-93. 2009
    ..The discovery of disease-causing mutations in RNAs is yielding a wealth of new therapeutic targets, and the growing understanding of RNA biology and chemistry is providing new RNA-based tools for developing therapeutics...
  5. ncbi IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA
    Marcella Calfon
    Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
    Nature 415:92-6. 2002
    ..Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes...
  6. ncbi Listening to silence and understanding nonsense: exonic mutations that affect splicing
    Luca Cartegni
    Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA
    Nat Rev Genet 3:285-98. 2002
    ..As the splicing mechanisms that depend on exonic signals are elucidated, new therapeutic approaches to treating certain genetic diseases can begin to be explored...
  7. ncbi The transcriptional landscape of the mammalian genome
    P Carninci
    Science 309:1559-63. 2005
    ..The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development...
  8. ncbi Improved splice site detection in Genie
    M G Reese
    Human Genome Informatics Group, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
    J Comput Biol 4:311-23. 1997
    ..In further splice site experiments, we also looked at correlations between splice site scores and intron and exon lengths, as well as at the effect of distance to the nearest splice site on false positive rates...
  9. ncbi Identification and characterization of a spinal muscular atrophy-determining gene
    S Lefebvre
    Unite de Recherches sur les Handicaps Genetiques de l Enfant, Institut National de la Sante et de la Recherche Medicale, Institut Necker, Hopital des Enfants Malades, Paris, France
    Cell 80:155-65. 1995
    ..These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene...
  10. ncbi The SR protein family of splicing factors: master regulators of gene expression
    Jennifer C Long
    Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh EH42XU, UK
    Biochem J 417:15-27. 2009
    ..Here, we will review the current literature to demonstrate how SR proteins are emerging as one of the master regulators of gene expression...
  11. ncbi Messenger-RNA-binding proteins and the messages they carry
    Gideon Dreyfuss
    Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    Nat Rev Mol Cell Biol 3:195-205. 2002
    ..These proteins communicate crucial information to the translation machinery for the surveillance of nonsense mutations and for mRNA localization and translation...
  12. pmc U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation
    Daisuke Kaida
    Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6148, USA
    Nature 468:664-8. 2010
    ..These findings reveal a critical splicing-independent function for U1 snRNP in protecting the transcriptome, which we propose explains its overabundance...
  13. ncbi Functional diversity of the hnRNPs: past, present and perspectives
    Siew Ping Han
    University of Queensland, Brisbane, Australia
    Biochem J 430:379-92. 2010
    ..Hence, we review the current literature to examine hnRNP diversity, and discuss how this impacts upon approaches to the classification of RNA-binding proteins in general...
  14. ncbi Pre-mRNA splicing: awash in a sea of proteins
    Melissa S Jurica
    Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    Mol Cell 12:5-14. 2003
    ..Another recurring theme regards the dynamic nature of spliceosomal complexes, which may be even more intricate than previously thought...
  15. pmc A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing
    Gwendolyn M Wilmes
    Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, Genentech Hall, San Francisco, CA 94143 2200, USA
    Mol Cell 32:735-46. 2008
    ..Finally, we show that Csn12 plays a role in pre-mRNA splicing, which is independent of other signalosome components. Thus, Sem1 is involved in three separate and functionally distinct complexes...
  16. ncbi Human mRNA export machinery recruited to the 5' end of mRNA
    Hong Cheng
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 127:1389-400. 2006
    ..As a consequence, the mRNA would be exported in a 5' to 3' direction through the nuclear pore, as observed in early electron micrographs of giant Balbiani ring mRNPs...
  17. pmc ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43
    Eveline S Arnold
    Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 110:E736-45. 2013
    ..Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage...
  18. ncbi Dynamic protein-protein interaction wiring of the human spliceosome
    Anna Hegele
    Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany
    Mol Cell 45:567-80. 2012
    ..Our data provide extensive information about the spliceosomal protein interaction network and its dynamics...
  19. pmc ESEfinder: A web resource to identify exonic splicing enhancers
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA
    Nucleic Acids Res 31:3568-71. 2003
    ....
  20. pmc A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains
    John N Hutchinson
    Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    BMC Genomics 8:39. 2007
    ..To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment...
  21. 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...
  22. ncbi The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response
    C Sidrauski
    Department of Biochemistry and Biophysics, University of California, School of Medicine, San Francisco 94143 0448, USA
    Cell 90:1031-9. 1997
    ..The addition of purified tRNA ligase completes splicing; we therefore have reconstituted HAC1 mRNA splicing in vitro from purified components...
  23. ncbi Local dystrophin restoration with antisense oligonucleotide PRO051
    Judith C van Deutekom
    Department of Human and Clinical Genetics, Leiden University Medical Center, The Netherlands
    N Engl J Med 357:2677-86. 2007
    ..We explored the safety, adverse-event profile, and local dystrophin-restoring effect of a single, intramuscular dose of an antisense oligonucleotide, PRO051, in patients with this disease...
  24. pmc SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing
    Zhenxi Zhang
    Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6148, USA
    Cell 133:585-600. 2008
    ..These findings reveal a key role for the SMN complex in RNA metabolism and in splicing regulation and indicate that SMA is a general splicing disease that is not restricted to motor neurons...
  25. pmc Understanding splicing regulation through RNA splicing maps
    Joshua T Witten
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK, CB2 0QH
    Trends Genet 27:89-97. 2011
    ..of protein-RNA interactions have been combined with assays of the global effects of RBPs on splicing to create RNA splicing maps...
  26. pmc Role of RNA structure in regulating pre-mRNA splicing
    M Bryan Warf
    Institute of Molecular Biology, and Department of Chemistry, University of Oregon, Eugene, Oregon 97403, USA
    Trends Biochem Sci 35:169-78. 2010
    ..Recent reports have identified proteins and small molecules that can regulate splicing by modulating RNA structures, thereby expanding our knowledge of the mechanisms used to regulate splicing...
  27. ncbi Global analysis of nascent RNA reveals transcriptional pausing in terminal exons
    Fernando Carrillo Oesterreich
    Max Planck Institute of Molecular Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
    Mol Cell 40:571-81. 2010
    ..The discovery of terminal exon pausing demonstrates functional coupling of transcription and splicing near gene ends...
  28. ncbi Nonsense-mediated mRNA decay (NMD) mechanisms
    Saverio Brogna
    University of Birmingham, School of Biosciences, Edgbaston, Birmingham B15 2TT, UK
    Nat Struct Mol Biol 16:107-13. 2009
    ..Here we discuss the limitations of the new NMD model and the EJC concept; we argue that neither satisfactorily accounts for all of the available data and offer a new model to test in future studies...
  29. ncbi Mobile group II introns
    Alan M Lambowitz
    Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Texas 78712, USA
    Annu Rev Genet 38:1-35. 2004
    ..After DNA insertion, the introns remove themselves by protein-assisted, autocatalytic RNA splicing, thereby minimizing host damage...
  30. pmc Rates of in situ transcription and splicing in large human genes
    Jarnail Singh
    Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Nat Struct Mol Biol 16:1128-33. 2009
    ..These results show that the expression of large genes is unexpectedly rapid and efficient...
  31. pmc Large-scale proteomic analysis of the human spliceosome
    Juri Rappsilber
    Protein Interaction Laboratory in the Center of Experimental Bioinformatics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK 5230 Odense M, Denmark
    Genome Res 12:1231-45. 2002
    ..This investigation provides the most detailed inventory of human spliceosome-associated factors to date, and the data indicate a number of interesting links coordinating splicing with other steps in the gene expression pathway...
  32. ncbi Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1
    Neal N Iwakoshi
    Department of Immunology and Infectious Diseases, Harvard School of Public Health 651 Huntington Avenue, Boston, Massachusetts 02115 6017, USA
    Nat Immunol 4:321-9. 2003
    ..We also show that XBP-1 is involved in controlling the production of interleukin-6, a cytokine that is essential for plasma cell survival. Thus, signals upstream and downstream of XBP-1 integrate plasma cell differentiation with the UPR...
  33. pmc A systematic characterization of Cwc21, the yeast ortholog of the human spliceosomal protein SRm300
    May Khanna
    Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada
    RNA 15:2174-85. 2009
    ..Together, the results suggest multiple functions for Cwc21/SRm300 in the splicing process, including an important role in the activation of splicing in association with Isy1...
  34. pmc A comprehensive analysis of prognostic signatures reveals the high predictive capacity of the proliferation, immune response and RNA splicing modules in breast cancer
    Fabien Reyal
    Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Breast Cancer Res 10:R93. 2008
    ..we address the following issues: Do these signatures perform similarly? Are there (common) molecular processes reported by these signatures? Can better prognostic predictors be constructed based on these identified molecular processes?..
  35. pmc Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing
    Robert J Sims
    Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA
    Mol Cell 28:665-76. 2007
    ..These findings suggest that methylated H3K4 serves to facilitate the competency of pre-mRNA maturation through the bridging of spliceosomal components to H3K4me3 via CHD1...
  36. pmc Prp8 protein: at the heart of the spliceosome
    Richard J Grainger
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, King s Buildings, Mayfield Road, Edinburgh EH9 3JR, United Kingdom
    RNA 11:533-57. 2005
    ....
  37. pmc Splicing-dependent RNA polymerase pausing in yeast
    Ross D Alexander
    Wellcome Trust Centre for Cell Biology, University of Edinburgh, King s Buildings, Edinburgh EH9 3JR, UK
    Mol Cell 40:582-93. 2010
    ..Phosphorylated polymerase also accumulates around the 3' splice sites of constitutively expressed, endogenous yeast genes. We propose that transcriptional pausing is imposed by a checkpoint associated with cotranscriptional splicing...
  38. ncbi How introns influence and enhance eukaryotic gene expression
    Hervé Le Hir
    Howard Hughes Medical Institute, Department of Biochemistry, MS009 Brandeis University, Waltham, MA 02454, USA
    Trends Biochem Sci 28:215-20. 2003
    ..A rudimentary understanding of these effects can prove invaluable to researchers interested in optimizing transgene expression in eukaryotic systems...
  39. ncbi A muscleblind knockout model for myotonic dystrophy
    Rahul N Kanadia
    Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, Gainesville, FL 32610, USA
    Science 302:1978-80. 2003
    ..Here, we show that disruption of the mouse Mbnl1 gene leads to muscle, eye, and RNA splicing abnormalities that are characteristic of DM disease...
  40. ncbi Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability
    Xialu Li
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Cell 122:365-78. 2005
    ..Our results support a model by which recruitment of ASF/SF2 to nascent transcripts by RNA polymerase II prevents formation of mutagenic R loop structures...
  41. ncbi A transgenic mouse model for monitoring endoplasmic reticulum stress
    Takao Iwawaki
    Laboratory for Cell Recovery Mechanisms, Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Nat Med 10:98-102. 2004
    ..We used transgenic animals expressing the ER stress indicator to show that it can be used to monitor physiological and pathological ER stress in vivo...
  42. pmc Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery
    Brian D Freibaum
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105 3678, USA
    J Proteome Res 9:1104-20. 2010
    ..Finally, we found numerous TDP-43 interactors that are known components of stress granules, and indeed, we find that TDP-43 is also recruited to stress granules...
  43. ncbi Crosstalk between mRNA 3' end processing and transcription initiation
    Christophe K Mapendano
    Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology, Aarhus University, C F Møllers Allé 3, Building 1130, DK 8000 Aarhus, Denmark
    Mol Cell 40:410-22. 2010
    ..Our data demonstrate that 3' end formation stimulates transcription initiation and suggest that coordinated recycling of factors from a gene terminator back to the promoter is essential for sustaining continued transcription...
  44. pmc Neuronal Elav-like (Hu) proteins regulate RNA splicing and abundance to control glutamate levels and neuronal excitability
    Gulayse Ince-Dunn
    Laboratory of Molecular Neuro Oncology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Neuron 75:1067-80. 2012
    ..The genome-wide analysis of nElavl targets reveals that one function of neuron-specific RNABPs is to control excitation-inhibition balance in the brain...
  45. ncbi Impaired minor tri-snRNP assembly generates differential splicing defects of U12-type introns in lymphoblasts derived from a type I SMA patient
    Nawal Boulisfane
    Institut de Génétique Moléculaire de Montpellier IGMM, CNRS UMR 5535 IFR122, Université Montpellier I and II, 1919 Route de Mende, 34293 Montpellier Cedex 5, France
    Hum Mol Genet 20:641-8. 2011
    ..Our results suggest that SMA might result from the inefficient splicing of one or only a few pre-mRNAs carrying minor introns and coding for proteins required for motor neurons function and/or organization...
  46. pmc The in vivo kinetics of RNA polymerase II elongation during co-transcriptional splicing
    Yehuda Brody
    The Mina and Everard Goodman Faculty of Life Sciences and Institute of Nanotechnology, Bar Ilan University, Ramat Gan, Israel
    PLoS Biol 9:e1000573. 2011
    ..This suggests that the polymerase is released from chromatin prior to the completion of splicing, and the pre-mRNA is post-transcriptionally processed while still tethered to chromatin near the gene end...
  47. pmc Splicing promotes rapid and efficient mRNA export in mammalian cells
    Patricia Valencia
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:3386-91. 2008
    ..We conclude that splicing promotes mRNA export in mammalian cells and that the functional coupling between splicing and mRNA export is a conserved and general feature of gene expression in higher eukaryotes...
  48. ncbi Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA
    Daisuke Kaida
    Chemical Genetics Laboratory, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Nat Chem Biol 3:576-83. 2007
    ..Thus, the inhibition of pre-mRNA splicing during early steps involving SF3b allows unspliced mRNA leakage and translation...
  49. pmc Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome
    Yang Bian
    Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Hum Mol Genet 18:1229-37. 2009
    ..These observations open the door to the discovery of novel therapies based on PTB overexpression and to detecting possible untoward effects of the overexpression...
  50. ncbi The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome
    Patrizia Fabrizio
    Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Gottingen, Germany
    Mol Cell 36:593-608. 2009
    ..Electron microscopy reveals high-quality images of yeast spliceosomes at defined functional stages, indicating that they are well-suited for three-dimensional structure analyses...
  51. ncbi Nuclearly encoded splicing factors implicated in RNA splicing in higher plant organelles
    Andéol Falcon de Longevialle
    Unité Mixte de Recherche en Génomique Végétale Institut National de la Recherche Agronomique Centre National de la Recherche Scientifique Université d Evry Val d Essonne, 91057 Evry, France
    Mol Plant 3:691-705. 2010
    ..In particular, RNA maturation, including RNA splicing, is highly dependent on nuclearly encoded splicing factors...
  52. ncbi Splicing regulation in neurologic disease
    Donny D Licatalosi
    Howard Hughes Medical Institute, Laboratory of Molecular Neuro Oncology, The Rockefeller University, New York, New York 10021, USA
    Neuron 52:93-101. 2006
    ..This review considers the evidence that defects in regulation of splicing may underlie many types of human neurologic diseases...
  53. ncbi SR proteins function in coupling RNAP II transcription to pre-mRNA splicing
    Rita Das
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 26:867-81. 2007
    ..Thus, these factors readily out-compete inhibitory hnRNP proteins, resulting in efficient spliceosome assembly on nascent RNAP II transcripts...
  54. ncbi Specific alterations of U1-C protein or U1 small nuclear RNA can eliminate the requirement of Prp28p, an essential DEAD box splicing factor
    J Y Chen
    Department of Molecular Genetics, Ohio State University, Columbus, OH 43210, USA
    Mol Cell 7:227-32. 2001
    ..Thus, in addition to unwinding RNA, the DExD/H box proteins may affect RNA-RNA rearrangements by antagonizing specific RNA-stabilizing proteins...
  55. pmc IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response
    Kyungho Lee
    Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
    Genes Dev 16:452-66. 2002
    ..Both processing of ATF6 and IRE1alpha-mediated splicing of XBP1 mRNA are required for full activation of the UPR...
  56. pmc Functional integration of transcriptional and RNA processing machineries
    Shatakshi Pandit
    Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0651, United States
    Curr Opin Cell Biol 20:260-5. 2008
    ....
  57. pmc Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution
    Daniel A Pomeranz Krummel
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Nature 458:475-80. 2009
    ..The structure of U1 snRNP provides insights into U1 snRNP assembly and suggests a possible mechanism of 5'-splice-site recognition...
  58. ncbi Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1
    Luca Cartegni
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Nat Genet 30:377-84. 2002
    ..The abrogation of the SF2/ASF-dependent ESE is the basis for inefficient inclusion of exon 7 in SMN2, resulting in the spinal muscular atrophy phenotype...
  59. ncbi TDP-43 binds heterogeneous nuclear ribonucleoprotein A/B through its C-terminal tail: an important region for the inhibition of cystic fibrosis transmembrane conductance regulator exon 9 splicing
    Emanuele Buratti
    International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
    J Biol Chem 280:37572-84. 2005
    ..Finally, through splicing complex analysis, we show that splicing inhibition mediated by TDP-43 occurs at the earliest stages of spliceosomal assembly...
  60. ncbi Crystal structure of a self-spliced group II intron
    Navtej Toor
    Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, Bass Building, New Haven, CT 06511, USA
    Science 320:77-82. 2008
    ..Structural and functional analogies support the hypothesis that group II introns and the spliceosome share a common ancestor...
  61. pmc The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing
    M Bryan Warf
    Institute of Molecular Biology and Department of Chemistry, University of Oregon, Eugene, OR 97403, USA
    Proc Natl Acad Sci U S A 106:9203-8. 2009
    ..Thus, U2AF65 binding can be blocked either by MBNL1 binding or by the stabilization of RNA secondary structure...
  62. pmc Transcription-mediated gene fusion in the human genome
    Pinchas Akiva
    Compugen Ltd, Tel Aviv 69512, Israel
    Genome Res 16:30-6. 2006
    ..Finally, we provide evidence that transcription-induced chimerism can be a mechanism contributing to the evolution of protein complexes...
  63. pmc Splicing regulation: from a parts list of regulatory elements to an integrated splicing code
    Zefeng Wang
    Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    RNA 14:802-13. 2008
    ..Here, we summarize the current state of knowledge of splicing cis-regulatory elements and their context-dependent effects on splicing, emphasizing recent global/genome-wide studies and open questions...
  64. pmc The network of protein-protein interactions within the human U4/U6.U5 tri-snRNP
    Sunbin Liu
    Department of Cellular Biochemistry, MPI of Biophysical Chemistry, Gottingen, Germany
    RNA 12:1418-30. 2006
    ..Taken together, data presented here provide a detailed picture of the network of protein interactions within the human tri-snRNP...
  65. pmc The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila
    Katsutomo Okamura
    Memorial Sloan Kettering Cancer Center, Department of Developmental Biology, 1275 York Ave, Box 252, New York, NY 10021, USA
    Cell 130:89-100. 2007
    ..These findings reveal that mirtrons are an alternate source of miRNA-type regulatory RNAs...
  66. pmc A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy
    Matteo Ruggiu
    Department of Pathology and Cell Biology, Columbia University, New York, New York, USA
    Mol Cell Biol 32:126-38. 2012
    ..These findings suggest a mechanism to explain the selective vulnerability of motor neurons to loss of SMN1...
  67. pmc The splicing regulator Rbfox2 is required for both cerebellar development and mature motor function
    Lauren T Gehman
    Molecular Biology Institute, University of California at Los Angeles, CA 90095, USA
    Genes Dev 26:445-60. 2012
    ..Rbfox2 is subsequently required with Rbfox1 to maintain mature neuronal physiology, specifically Purkinje cell pacemaking, through their shared control of sodium channel transcript splicing...
  68. ncbi Primary microRNA transcripts are processed co-transcriptionally
    Mariangela Morlando
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
    Nat Struct Mol Biol 15:902-9. 2008
    ....
  69. pmc Expanded CUG repeats Dysregulate RNA splicing by altering the stoichiometry of the muscleblind 1 complex
    Sharan Paul
    Department of Biochemistry, University of Southern California, Los Angeles, California 90033, USA
    J Biol Chem 286:38427-38. 2011
    ..Thus expression of expanded CUG repeats alters the stoichiometry of MBNL1(CUG) complexes to allow both the reinforcement and expansion of RNA processing defects...
  70. pmc The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay
    H Le Hir
    Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA
    EMBO J 20:4987-97. 2001
    ..Finally, we show that the composition of the EJC is dynamic in vivo and is subject to significant evolution upon mRNA export to the cytoplasm...
  71. ncbi A Pre-mRNA degradation pathway that selectively targets intron-containing genes requires the nuclear poly(A)-binding protein
    Caroline Lemieux
    RNA Group, Department of Biochemistry, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada
    Mol Cell 44:108-19. 2011
    ..Our findings unveil a layer of regulation in the nucleus in which the turnover of specific pre-mRNAs, besides the turnover of mature mRNAs, is used to control gene expression...
  72. pmc Systematic two-hybrid and comparative proteomic analyses reveal novel yeast pre-mRNA splicing factors connected to Prp19
    Liping Ren
    Howard Hughes Medical Institute, Vanderbilt University, Nashville, Tennessee, corrected United States of America
    PLoS ONE 6:e16719. 2011
    ..Our multi-faceted approach has revealed new low abundance splicing factors connected to NTC function, provides evidence for distinct Prp19 containing complexes, and underscores the role of the Prp19 WD40 domain as a splicing scaffold...
  73. pmc Mammalian mirtron genes
    Eugene Berezikov
    Hubrecht Institute, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    Mol Cell 28:328-36. 2007
    ..This notion is supported by our observation of several clade-specific features of mammalian and invertebrate mirtrons...
  74. ncbi Total RNA sequencing reveals nascent transcription and widespread co-transcriptional splicing in the human brain
    Adam Ameur
    Department of Immunology, Genetics and Pathology, Science for Life Laboratory Uppsala, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
    Nat Struct Mol Biol 18:1435-40. 2011
    ..Our data show that sequencing of total RNA provides unique insight into the transcriptional processes in the cell, with particular importance for normal brain development...
  75. pmc Removal of a single alpha-tubulin gene intron suppresses cell cycle arrest phenotypes of splicing factor mutations in Saccharomyces cerevisiae
    C Geoffrey Burns
    Howard Hughes Medical Institute, Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Mol Cell Biol 22:801-15. 2002
    ....
  76. pmc Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions
    Dev M Bhatt
    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Cell 150:279-90. 2012
    ....
  77. ncbi Cotranscriptional exon skipping in the genotoxic stress response
    Martin Dutertre
    Institut National de Santé et de Recherche Médicale U590, Centre Leon Berard, Lyon, France
    Nat Struct Mol Biol 17:1358-66. 2010
    ..These data demonstrate genotoxic stress-induced alteration of the communication between the transcriptional and splicing machineries, which results in widespread exon skipping and plays a central role in the genotoxic stress response...
  78. ncbi Spliceosomal cleavage generates the 3' end of telomerase RNA
    Jessica A Box
    Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA
    Nature 456:910-4. 2008
    ..We establish that 3' end processing of TER1 is critical for telomerase function and describe a previously unknown mechanism for RNA maturation that uses the ability of the spliceosome to mediate site-specific cleavage...
  79. ncbi Comprehensive analysis of archaeal tRNA genes reveals rapid increase of tRNA introns in the order thermoproteales
    Junichi Sugahara
    Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan
    Mol Biol Evol 25:2709-16. 2008
    ..The sequences and secondary structures of the tRNA genes and their bulge-helix-bulge motifs were registered in SPLITSdb (http://splits.iab.keio.ac.jp/splitsdb/), a novel and comprehensive database for archaeal tRNA genes...
  80. pmc High-density yeast-tiling array reveals previously undiscovered introns and extensive regulation of meiotic splicing
    Kara Juneau
    Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 104:1522-7. 2007
    ..This robust methodology can be used to explore environmentally distinct splicing responses and should be readily adaptable to the study of other organisms, including humans...
  81. pmc Heat induces the splicing by IRE1 of a mRNA encoding a transcription factor involved in the unfolded protein response in Arabidopsis
    Yan Deng
    Plant Sciences Institute, Iowa State University, Ames, IA 50011, USA
    Proc Natl Acad Sci U S A 108:7247-52. 2011
    ..agents, Arabidopsis seedlings mitigate stress damage by activating ER-associated transcription factors and a RNA splicing factor, IRE1b...
  82. pmc Origins of recently gained introns in Caenorhabditis
    Avril Coghlan
    Department of Genetics, Smurfit Institute, University of Dublin, Trinity College, Dublin 2, Ireland
    Proc Natl Acad Sci U S A 101:11362-7. 2004
    ..All of these similarities involve minisatellites or palindromes in the intron sequences. Our results suggest that at least some of the intron gains were caused by reverse splicing of a preexisting intron...
  83. ncbi The mammalian nonsense-mediated mRNA decay pathway: to decay or not to decay! Which players make the decision?
    Ana Luisa Silva
    Centro de Genética Humana, Instituto Nacional de Saude Dr Ricardo Jorge, Lisboa, Portugal
    FEBS Lett 583:499-505. 2009
    ....
  84. ncbi SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs
    Xiaoju Max Ma
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Cell 133:303-13. 2008
    ..Thus, SKAR-mediated recruitment of activated S6K1 to newly processed mRNPs serves as a conduit between mTOR checkpoint signaling and the pioneer round of translation when cells exist in conditions supportive of protein synthesis...
  85. ncbi hnRNP A1 proofreads 3' splice site recognition by U2AF
    João Paulo Tavanez
    Centre de Regulacio Genomica, Dr Aiguader 88, 08003 Barcelona, Spain Universitat Pompeu Fabra, Dr Aiguader 88, 08003 Barcelona, Spain
    Mol Cell 45:314-29. 2012
    ..Consistent with the functional relevance of this activity for splicing, proofreading assays reveal a role for hnRNP A1 in U2AF-mediated recruitment of U2 snRNP to the pre-mRNA...
  86. ncbi Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA
    Patrick Edery
    Hospices Civils de Lyon, Service de Cytogénétique Constitutionnelle, Bron, F 69677, France
    Science 332:240-3. 2011
    The spliceosome, a ribonucleoprotein complex that includes proteins and small nuclear RNAs (snRNAs), catalyzes RNA splicing through intron excision and exon ligation to produce mature messenger RNAs, which, in turn serve as templates for ..
  87. pmc Splice-site mutations cause Rrp6-mediated nuclear retention of the unspliced RNAs and transcriptional down-regulation of the splicing-defective genes
    Andrea B Eberle
    Department of Molecular Biology and Functional Genomics, Stockholm University, Stockholm, Sweden
    PLoS ONE 5:e11540. 2010
    ..The exosome subunit Rrp6 is required for this checkpoint in Saccharomyces cerevisiae, but it is not known whether Rrp6 also plays a role in mRNA surveillance in higher eukaryotes...
  88. pmc Intron-dominated genomes of early ancestors of eukaryotes
    Eugene V Koonin
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
    J Hered 100:618-23. 2009
    ..An organism with such an unusual genome architecture could survive only under conditions of a severe population bottleneck...
  89. ncbi De novo origin of new genes with introns in Plasmodium vivax
    Zefeng Yang
    Department of Biology, East Carolina University, Greenville, NC 27858, USA
    FEBS Lett 585:641-4. 2011
    ..We discuss the potential mechanisms for intron formation in these genes and propose that intronization be considered in the formation of de novo originated genes...
  90. ncbi Splicing segregation: the minor spliceosome acts outside the nucleus and controls cell proliferation
    Harald König
    Forschungszentrum Karlsruhe GmbH, Institut für Toxikologie und Genetik, Postfach 3640, 76021 Karlsruhe, Germany
    Cell 131:718-29. 2007
    ..The segregation offers a mechanism accounting for spliceosome evolution in a single lineage and provides a means for nucleus-independent control of gene expression...
  91. ncbi Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing
    Chi Zhang
    Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, USA
    J Biol Chem 278:35325-36. 2003
    ..that NCoA62/SKIP has properties that are consistent with those of nuclear receptor coactivators and with RNA spliceosome components, thus suggesting a potential role for NCoA62/SKIP in coupling VDR-mediated transcription to RNA splicing.
  92. pmc Proteasome inhibitors disrupt the unfolded protein response in myeloma cells
    Ann Hwee Lee
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115 6017, USA
    Proc Natl Acad Sci U S A 100:9946-51. 2003
    ..Identification of compounds that target the activity of IRE1 alpha/XBP-1 may yield novel therapies for the treatment of multiple myeloma and other malignancies that rely on an intact UPR...
  93. pmc Genomic features defining exonic variants that modulate splicing
    Adam Woolfe
    Genomic Functional Analysis Section, National Human Genome Research Institute, National Institutes of Health, Rockville, Maryland 20892, USA
    Genome Biol 11:R20. 2010
    ..In addition, little is known about which computational prediction approaches, such as those involving exonic splicing enhancers and exonic splicing silencers, are most informative...
  94. pmc U12DB: a database of orthologous U12-type spliceosomal introns
    Tyler S Alioto
    Genome Bioinformatics Laboratory, Center for Genomic Regulation, Doctor Aiguader 88, 08003 Barcelona, Spain
    Nucleic Acids Res 35:D110-5. 2007
    ..Public access to the U12DB is available at http://genome.imim.es/cgi-bin/u12db/u12db.cgi...
  95. ncbi Mystery of intron gain: new data and new models
    Scott William Roy
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20892, USA
    Trends Genet 25:67-73. 2009
    ..In addition, we introduce two potential mechanisms for intron creation, based on hybrid RNA-DNA reverse splicing and on template switching errors by reverse transcriptase...
  96. ncbi Chromatin organization marks exon-intron structure
    Schraga Schwartz
    Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
    Nat Struct Mol Biol 16:990-5. 2009
    ..Our results suggest an RNA polymerase II-mediated cross-talk between chromatin structure and exon-intron architecture, implying that exon selection may be modulated by chromatin structure...
  97. pmc Chromatin density and splicing destiny: on the cross-talk between chromatin structure and splicing
    Schraga Schwartz
    Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
    EMBO J 29:1629-36. 2010
    ..In this review we discuss evidence for the coupling between transcription and splicing, focusing on recent findings suggesting a link between chromatin structure and splicing, and highlighting challenges this emerging field is facing...
  98. pmc Messenger RNA targeting to endoplasmic reticulum stress signalling sites
    TOMAS ARAGON
    Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, California 94158 2517, USA
    Nature 457:736-40. 2009
    ..Translational repression afforded by the intron fulfils this requirement for HAC1 mRNA. Recruitment of mRNA to signalling centres provides a new paradigm for the control of eukaryotic gene expression...
  99. ncbi hnRNP proteins and splicing control
    Rebeca Martinez-Contreras
    Departement de Microbiologie et d Infectiologie, Universite de Sherbrooke, Quebec, Canada
    Adv Exp Med Biol 623:123-47. 2007
    ..Thus, hnRNP proteins utilize a variety of strategies to control splice site selection in a manner that is important for both alternative and constitutive pre-mRNA splicing...
  100. ncbi DEAD-box proteins: the driving forces behind RNA metabolism
    Sanda Rocak
    Departement de Biochimie Medicale, Centre Medical Universitaire, 1 rue Michel Servet, CH 1211 Geneva 4, Switzerland
    Nat Rev Mol Cell Biol 5:232-41. 2004
  101. ncbi Bypassing a kinase activity with an ATP-competitive drug
    Feroz R Papa
    Department of Medicine, University of California, San Francisco, CA 94143 2200, USA
    Science 302:1533-7. 2003
    ..Thus, rather than through phosphorylation per se, a conformational change in the kinase domain triggered by occupancy of the active site with a ligand leads to activation of all known downstream functions...

Research Grants66

  1. REGULATION OF GENE EXPRESSION BY DIETARY FAT
    Lisa M Salati; Fiscal Year: 2012
    ..of our studies on mechanisms by which fatty acids regulate gene expression, we discovered that the rate of RNA splicing is inhibited in liver and primary hepatocytes by dietary polyunsaturated fat and by arachidonic acid, ..
  2. Mechanisms of Splicing Regulation During Environmental Stress in Yeast
    Jaclyn C Greimann; Fiscal Year: 2012
    ..many molecular changes, or processing reactions, which alter its stability including 5'cap formation, RNA splicing and addition of a polyadenine tail...
  3. Functional characterization of the Bronx waltzer deafness gene
    Botond Banfi; Fiscal Year: 2013
    ..spliceosomal protein Ser/Arg-repetitive matrix 4 (SRRM4) in such a way that this protein fails to mediate key RNA splicing events necessary for the survival of inner hair cells and vestibular hair cells...
  4. The Role of RNA Splicing Factors in Retinal Degeneration
    Michael Farkas; Fiscal Year: 2012
    ..many genes have been implicated in the disease, we propose to investigate how mutations in genes required for RNA splicing cause dominant RP...
  5. ALS therapies and genomics for mutant TDP-43 and TLS/FUS
    Don W Cleveland; Fiscal Year: 2010
    ..In the normal context, both proteins have been linked to RNA transcription and alternative RNA splicing (FUS/TLS is an integral component of the spliceosome)...
  6. Role of Coxiella burnetii group I introns in growth modulation
    Michael F Minnick; Fiscal Year: 2010
    ..Cofactors will be analyzed by varying the RNA splicing buffer. Two final goals will follow expression of a potential homing endonuclease (HE) encoded by Cbu...
  7. SPLICING OF MRNA PRECURSORS
    Michael R Green; Fiscal Year: 2013
    ..most eukaryotic genes (precursor mRNAs;pre-mRNAs) contain intervening sequences (introns) that are removed by RNA splicing in a two-step pathway...
  8. Functional Selection of Novel Ligands from the Neuroendocrine Secretome
    David Larocca; Fiscal Year: 2010
    ..Alterations in RNA splicing and protein processing result in the much higher complexity than is evident in the human transcriptome and in ..
  9. Nuclear Function of Abl in DNA Damage Response
    Jean Y J Wang; Fiscal Year: 2012
    ..phosphorylation of the C-terminal repeated domain (CTD) of RNA polymerase II, we have found that Abl regulates RNA splicing in genotoxin-treated cells...
  10. Association of a common variant of the PPAP2B gene with cardiovascular disease.
    Andrew J Morris; Fiscal Year: 2013
    ..levels in white blood cells and arterial tissue and by examining the consequences, of the polymorphism on RNA splicing and stability. Secondly, we will establish a mechanistic role for LPP3 in experimental atherosclerosis...
  11. Alternative Splicing of the Insulin Receptor Gene
    NICHOLAS J WEBSTER; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Summary and Abstract RNA splicing is the process of removal of intronic sequences from the primary RNA transcript before the final mRNA is generated...
  12. Identification, Discovery, and Public Archiving of RNA Structural Motifs
    Shaojie Zhang; Fiscal Year: 2013
    ..RNAs play many functional roles in biological processes, such as catalysis, gene expression regulation and RNA splicing. The various roles played by non-coding RNA are determined by their character- istic structure...
  13. SMN Control of snRNP Biogenesis: Role in RNA Splicing and Motor Neuron Survival
    Livio Pellizzoni; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Project Summary Regulation of RNA splicing is the primary mechanism responsible for generating the proteome diversity and phenotypic complexity of humans...
  14. Role of Splicing Factors in Breast Cancer
    OLGA ANCZUKOW-CAMARDA; Fiscal Year: 2013
    ..Mikala Egeblad. This training will complement my previous expertise in breast cancer research and RNA splicing mechanisms...
  15. Regulation of caspase 9 RNA splicing in NSCLC cancer
    Charles E Chalfant; Fiscal Year: 2013
    ....
  16. The Role of Caspase 9b Expression in NSCLC Survival/Chemotherapeutic Sensitivity
    Charles E Chalfant; Fiscal Year: 2013
    ..will determine the mechanisms and cell signaling pathways regulated by the survival product of caspase 9 RNA splicing, caspase 9b. These studies will also examine naturally occurring tumor suppression pathways (e.g...
  17. Antisense oligonucleotide treatment for myotonic dystrophy
    Charles A Thornton; Fiscal Year: 2013
    ..in nuclear foci and initiates a complex cascade of downstream events, such as, defects in the regulation of RNA splicing. An attractive therapeutic approach, therefore, is to attack the problem at its root cause, by accelerating the ..
  18. Human Osteoprogenitor Control by Hepatocyte Growth Factor and Vitamin D
    Guy Howard; Fiscal Year: 2013
    ..on alterations of p63 differential gene expression products resulting from alternative promoter selection and RNA splicing changes...
  19. MECHANISMS OF ENHANCER DEPENDENT SPLICE SITE ACTIVATION
    Klemens J Hertel; Fiscal Year: 2013
    ..previous funding period;charting highly significant correlations between alternative splicing and cis-acting RNA splicing elements, the discovery of a mechanism that describes position-dependent activities of splicing regulators, and ..
  20. RNA Binding Protein CUGBP2 in Intestinal Epithelium
    Shrikant Anant; Fiscal Year: 2010
    ..We will also determine the effect of these interactions on CUGBP2 mediated RNA splicing, mRNA stability and translation regulation...
  21. Pathogenic Mechanisms in Fragile X Tremor Ataxia Syndrome
    Peter K Todd; Fiscal Year: 2013
    ..dysregulation of the FMR1 gene in cis and RNA mediated gain of function toxicity leading to anomalous RNA splicing events and alterations in protein quality control pathways...
  22. MOLECULAR MECHANISMS OF THE MYOTONIC DYSTROPHY MUTATION
    MANI SUBRAMANIAM MAHADEVAN; Fiscal Year: 2013
    ..reproduced cardinal features of DM including myotonia, cardiac conduction abnormalities, DM histopathology and RNA splicing defects in the absence of detectable nuclear inclusions...
  23. THE ORGANIZATION OF ANIMAL CELL NUCLEI
    Joseph G Gall; Fiscal Year: 2013
    ..These studies could reveal aspects of RNA transcription and processing that are missed by conventional in vitro molecular studies. ..
  24. 2011 Eukaryotic mRNA Processing Conference
    David J Stewart; Fiscal Year: 2011
    ..scientists are studying how this messenger RNA processing occurs and is controlled, helped by the fact that the RNA splicing machinery is highly conserved between yeast and humans...
  25. Molecular Mechanism of Leukemogenesis Involving AML1-ETO
    Dong Er Zhang; Fiscal Year: 2013
    ..Interestingly, multiple forms of AML1-ETO are present in t(8;21) leukemia samples due to alternative RNA splicing and deletion mutations...
  26. Cell Biology, Genetics, and Biochemistry Training Program
    DAVID OWEN MORGAN; Fiscal Year: 2013
    ..trafficking, cytoskeletal organization, protein and nucleic acid folding and structure, DNA replication, RNA splicing, transcriptional control, infectious disease, and various problems in molecular evolution...
  27. Structural/Functional Modularity in Nitric Oxide Synthase
    Linda J Roman; Fiscal Year: 2012
    ..NOS enzymes, and other products of these genes are expressed in various tissues as a result of alternative RNA splicing. L-Arginine is the natural substrate for NOS isoforms, producing L-citrulline and NO, which serves as a gaseous ..
  28. De Novo Methyltransferase Function in Chromatin and Cancer
    Keith D Robertson; Fiscal Year: 2013
    ..of these interactions in normal cells is to recruit DNA methylation to intragenic loci to regulate alternative RNA splicing. We will test this hypothesis with three specific aims...
  29. The role of the SF3B1 splicing factor in chronic lymphocytic leukemia
    CATHERINE JU YING WU; Fiscal Year: 2013
    ..Mutations in SF3B1 and modulation of RNA splicing are likely to represent a novel oncogenic process across hematologic malignancies and preferentially in ..
  30. Transcriptional elongation and splicing in human genes in situ
    Richard A Padgett; Fiscal Year: 2013
    ..These features represent an extreme challenge to the processes of transcription and RNA splicing. For RNA splicing, very large introns present the problem of identifying the correct splice sites and exons in ..
  31. Analysis of metazoan SAGA complex function in gene expression
    Jerry L Workman; Fiscal Year: 2013
    ..which when perturbed gives rise to spinocerebellar ataxia 7, and two splicing proteins that may link SAGA to RNA splicing. In the second aim, we propose to express epitope tagged versions of SAGA subunits in specific tissues and ..
  32. Biogenesis of Small Ribonucleoproteins
    A Gregory Matera; Fiscal Year: 2013
    ..As key elements of the spliceosome, the Sm-class small nuclear (sn)RNPs are essential for pre-messenger RNA splicing. Assembly into stable RNP particles is thought to be mediated by the Survival Motor Neuron (SMN) protein ..
  33. 2010 Post-Transcriptional Gene Regulation Biology of Gordon Research Conference
    Lynne E Maquat; Fiscal Year: 2010
    ..normally and in disease using immunoprecipitation followed by microarrays or high-throughput sequencing);RNA splicing catalysis, fidelity, regulation, and involvement in disease;RNA turnover, including nonsense-mediated mRNA ..
  34. Regulation, interaction, and inhibitor discovery of phosphodiesterases
    Hengming Ke; Fiscal Year: 2013
    ..genome encodes 21 PDE genes that are categorized into 11 families and express over 100 isoforms of proteins via RNA splicing. Selective inhibitors of PDEs have been studied as therapeutic agents for various human diseases...
  35. REGULATION OF GENE EXPRESSION IN CARTILAGE
    Linda Sandell; Fiscal Year: 2009
    ..insight into the regulation of chondrogenesis as it is becoming apparent that processes of transcription, RNA splicing and translation are tightly coordinated...
  36. Hu proteins as novel splicing regulators in neurons
    Hua Lou; Fiscal Year: 2013
    ..insights into the mechanisms that control tissue-specific, particularly neuron-specific, alternative RNA splicing and coupling of transcription and splicing...
  37. Hu proteins as novel splicing regulators in neurons
    Hua Lou; Fiscal Year: 2009
    ..insights into the mechanisms that control tissue-specific, particularly neuron-specific, alternative RNA splicing and coupling of transcription and splicing...
  38. REPLICATION OF SIMPLE DNA REPEATS
    Sergei M Mirkin; Fiscal Year: 2012
    ..responsible for gene repression in our system by studying the effects of various repeats on transcription, RNA splicing and RNA stability...
  39. REGULATION OF MRNA PROCESSING
    Phillip A Sharp; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Regulation at the stage of alternative RNA splicing is common in the expression of most genes in mammallian cells...
  40. Regulation of the v-Myb and c-Myb Oncoproteins
    Scott A Ness; Fiscal Year: 2010
    ..Furthermore, alternative RNA splicing produces at least a dozen different variants of human c-Myb protein with dramatically different activities...
  41. Adeno-associated Virus RNA Splicing and Polyadenylation
    David J Pintel; Fiscal Year: 2013
    ..We propose to expand this analysis in this proposal. The knowledge gained from our studies will advance our understanding of this important mechanism of gene expression in this important group of viruses. ..
  42. Specialized Program Of Research Excellence (SPORE) in Leukemia
    Daniel C Link; Fiscal Year: 2013
    ..we identified several novel recurring mutations of genes involved in DNA methylation (DNMT3A and IDH1) and RNA splicing (U2AF1). This basic research has led to the development of the following two translational SPORE projects...
  43. The Pathogenesis of RNA Splicing Factor RP
    Eric A Pierce; Fiscal Year: 2013
    ..long-term objectives of the proposed research are to improve our understanding of the pathogenesis of the RNA splicing factor forms of retinitis pigmentosa (RP) so that therapies for these blinding disorders can be developed...
  44. M.tuberculosis-induced Alternative Processing of IL12RB1 mRNA
    Richard Robinson; Fiscal Year: 2013
    ..different level of IL12R[unreadable]1 activity regulation - signal-mediated post-transcriptional alternative RNA splicing / polyadenylation - in humans...
  45. Targeted and global proteomic strategies for early breast cancer detection
    Susan J Fisher; Fiscal Year: 2011
    ..The targeted approaches will focus on cancer-specific proteins that result from aberrant RNA splicing. Candidate biomarkers will be validated using reverse phase protein arrays...
  46. PRODUCTION OF ALTERNATIVE FGF RECEPTOR FORMS IN TUMORS
    Gilbert J Cote; Fiscal Year: 2010
    ..in recent years, few studies have examined the impact and mechanisms responsible for aberrant changes in RNA splicing. Because previous studies have demonstrated the aberrant RNA splicing of numerous genes associated with GBM, ..
  47. COLD SPRING HARBOR LABORATORY CANCER RESEARCH CENTER
    Gregory J Hannon; Fiscal Year: 2013
    ..into DNA replication its coordination in normal and cancer cells, and established that aberrant alternative RNA splicing is an important oncogenic mechanism...
  48. Analyzing pre-mRNA splicing by deep sequencing of splice sites
    Jonathan P Staley; Fiscal Year: 2011
    ..information encoded in our DNA into the molecular workhorses of the cell requires an intermediate step, termed RNA splicing, in which interruptions of the information are deleted...
  49. Cytoplasmic Functions of Rbfox1, a Candidate Autism Gene
    Kelsey C Martin; Fiscal Year: 2013
    ..Rbfox1 binds a well-defined RNA sequence, (U)GCAUG, and functions in the nucleus as a regulator of RNA splicing. Rbfox1 itself is alternatively spliced into nuclear and cytoplasmic forms...
  50. Reproductive Hormones - Biological and Molecular Actions
    BERT W O'MALLEY; Fiscal Year: 2013
    ..chromatin remodeling, transcriptional initiation, RNA chain elongation, RNA splicing, termination, etc...
  51. GENE EXPRESSION IN SINGLE AGING NEURONS AND GLIA
    James H Eberwine; Fiscal Year: 2010
    ..Secondly, we have recently shown that dendrites have the capacity to modify RNAs though extra-nuclear RNA splicing. We will continue to investigate this phenomena by identifying endogenous RNAs that can be locally spliced in ..
  52. The Catalytic Mechanism of Nuclear Premessenger RNA Splicing by the Spliceosome
    Jonathan P Staley; Fiscal Year: 2013
    ..Given that at least 15% of human diseases result from errors in splicing, this work will also illuminate the inner workings of a machine that is essential to the well- being of humans. ..
  53. Correction of Hearing and Vestibular Defects in a Mouse Model for Deafness
    Michelle L Hastings; Fiscal Year: 2013
    ..We designed an ASO to correct an RNA splicing defect caused by a mutation in the USH1C gene that causes Usher syndrome in mice and humans...
  54. Computational and experimental modeling of RNA Splicing
    Michael Q Zhang; Fiscal Year: 2012
    ....
  55. Macromolecular Diffraction Resource: MacCHESS
    Richard A Cerione; Fiscal Year: 2013
    ..abstract_text> ..
  56. Elucidating the functions of Bud31, an essential gene in Myc-driven breast cancer
    Tiffany Y Hsu; Fiscal Year: 2013
    ..in cells stressed by MYC hyperactivation, to discover how excess MYC activity confers dependency on the RNA splicing machinery, and to exploit these vulnerabilities as therapeutic targets in MYC-driven breast cancers...
  57. Nanoplatform Delivery of MDA-7 and Brachytherapy for Treatment of Brain Tumors
    Michael D Shultz; Fiscal Year: 2013
    ..This project also aims to define a novel mechanism of enhanced therapeutic efficacy through Mcl-1 RNA splicing. The expression of Mcl-1 has been linked to a better prognosis for GBM patients as well as the sensitivity of ..
  58. Methods for purification of individual nuclear pre-messenger RNA-protein complexe
    Donald C Rio; Fiscal Year: 2013
    ..expertise of my lab in evaluating genome-wide patterns of alternative pre-mRNA splicing and the distribution of RNA splicing factors on nuclear pre-mRNAs...
  59. Characterization of RNA targets for the Drosophila protein Lark during oogenesis
    GERARD PATRICK MCNEIL; Fiscal Year: 2013
    ..regulation of gene expression and localization in the developing egg chamber, little is known about the role of RNA splicing. These experiments should provide evidence suggesting RNA splicing plays an important role in the regulation of ..
  60. The Identification and Manipulation of RNA Splicing Factor Regulators in Spinal M
    MALLORY ANN HAVENS; Fiscal Year: 2013
    ..abstract_text> ..
  61. RNA SPLICING IN ARCHAEA
    Ramesh Gupta; Fiscal Year: 2012
    ..Thus, the overall understanding of these processes in archaeal systems will help us understand similar processes in human systems under normal conditions, and the changes that may occur under diseased conditions. ..
  62. High Throughput Screen for Myotonic Dystrophy Type 1
    SITA contact REDDY; Fiscal Year: 2011
    ..Expression of CUGexp RNAs leads to abnormal RNA splicing, which in turn has been linked to the development of key features of DM1 pathology...
  63. MUTATION IDENTIFICATION IN HERITABLE CHONDRODYSTROPHIES
    Deborah Redford Badwal; Fiscal Year: 1993
    ..The molecular defects range from a single base changes and multi-exon deletions to abnormalities of RNA splicing. The type II collagen gene has many similarities to type I...
  64. METAL CARCINOGEN-INDUCED MUTATIONS IN MAMMALIAN GENES
    EDWIN MURPHY; Fiscal Year: 1992
    ..v-mos region is restricted to growth temperatures of 33degrees C and below by a conditionally defective viral RNA splicing event...
  65. RNA TERTIARY STRUCTURE AND PROTEIN INTERACTIONS
    W David Wilson; Fiscal Year: 1999
    ..b>RNA splicing, telomere synthesis and differentiation...
  66. Regulation of HIV-1 RNA Processing
    Massimo Caputi; Fiscal Year: 2007
    ..hnRNP H proteins have been shown to be necessary for HIV-1 RNA splicing in a series of in vitro experiments. They may also regulate RNA export and trafficking in infected cells...