alternative splicing

Summary

Summary: A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.

Top Publications

  1. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001
  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 Splicing in disease: disruption of the splicing code and the decoding machinery
    Guey Shin Wang
    Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Rev Genet 8:749-61. 2007
  4. pmc Expansion of the eukaryotic proteome by alternative splicing
    Timothy W Nilsen
    Center for RNA Molecular Biology, Department of Biochemistry, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
    Nature 463:457-63. 2010
  5. ncbi Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing
    Qun Pan
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada
    Nat Genet 40:1413-5. 2008
  6. pmc Alternative isoform regulation in human tissue transcriptomes
    Eric T Wang
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 456:470-6. 2008
  7. pmc Transcriptome genetics using second generation sequencing in a Caucasian population
    Stephen B Montgomery
    Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211 Switzerland
    Nature 464:773-7. 2010
  8. ncbi CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing
    Sanjeev Shukla
    Center for Cancer Research, Mouse Cancer Genetics Program, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
    Nature 479:74-9. 2011
  9. ncbi The evolutionary landscape of alternative splicing in vertebrate species
    Nuno L Barbosa-Morais
    Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
    Science 338:1587-93. 2012
  10. pmc The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation
    Vidisha Tripathi
    Department of Cell and Developmental Biology, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Mol Cell 39:925-38. 2010

Research Grants

  1. Pathogenesis of Myopathy in Models of Myotonic Dystrophy
    Charles Thornton; Fiscal Year: 2009
  2. Alternative processing and antisense regulation of thyroid hormone receptor mRNA
    STEPHEN MUNROE; Fiscal Year: 2007
  3. Mechanisms of Bronchial Myogenesis
    Lucia Schuger; Fiscal Year: 2005
  4. Genetics and Haloperidol Response
    Robert J Hitzemann; Fiscal Year: 2012
  5. BIOCHEMISTRY OF PRE-MRNA SPLICING
    Adrian R Krainer; Fiscal Year: 2010
  6. REGULATION OF GENE EXPRESSION BY DIETARY FAT
    Lisa M Salati; Fiscal Year: 2012
  7. Role of CD44 in experimental Multiple Sclerosis
    Mitzi Nagarkatti; Fiscal Year: 2013
  8. Molecular Mechanisms of Parvovirus Gene Expression and Replication
    Jianming Qiu; Fiscal Year: 2013
  9. Novel Collagen II Alternative Transcripts and Mouse Skeletal Development
    Audrey McAlinden; Fiscal Year: 2010
  10. Gene Transcription in SLE
    George C Tsokos; Fiscal Year: 2012

Detail Information

Publications373 found, 100 shown here

  1. ncbi Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy
    R S Savkur
    Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, USA
    Nat Genet 29:40-7. 2001
    ..Here we demonstrate that alternative splicing of the insulin receptor (IR) pre-mRNA is aberrantly regulated in DM1 skeletal muscle tissue, resulting in ..
  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 Splicing in disease: disruption of the splicing code and the decoding machinery
    Guey Shin Wang
    Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Rev Genet 8:749-61. 2007
    ..b>Alternative splicing generates a highly dynamic human proteome through networks of coordinated splicing events...
  4. pmc Expansion of the eukaryotic proteome by alternative splicing
    Timothy W Nilsen
    Center for RNA Molecular Biology, Department of Biochemistry, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA
    Nature 463:457-63. 2010
    ..It is now clear that the 'missing' information is in large part provided by alternative splicing, the process by which multiple different functional messenger RNAs, and therefore proteins, can be ..
  5. ncbi Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing
    Qun Pan
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada
    Nat Genet 40:1413-5. 2008
    We carried out the first analysis of alternative splicing complexity in human tissues using mRNA-Seq data. New splice junctions were detected in approximately 20% of multiexon genes, many of which are tissue specific...
  6. pmc Alternative isoform regulation in human tissue transcriptomes
    Eric T Wang
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Nature 456:470-6. 2008
    ..in which sequence reads are mapped to exon-exon junctions indicated that 92-94% of human genes undergo alternative splicing, 86% with a minor isoform frequency of 15% or more...
  7. pmc Transcriptome genetics using second generation sequencing in a Caucasian population
    Stephen B Montgomery
    Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, 1211 Switzerland
    Nature 464:773-7. 2010
    ..number of variants that influence the structure of mature transcripts indicating variants responsible for alternative splicing. Finally, measures of allele-specific expression allowed the identification of rare eQTLs and allelic ..
  8. ncbi CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing
    Sanjeev Shukla
    Center for Cancer Research, Mouse Cancer Genetics Program, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
    Nature 479:74-9. 2011
    b>Alternative splicing of pre-messenger RNA is a key feature of transcriptome expansion in eukaryotic cells, yet its regulation is poorly understood...
  9. ncbi The evolutionary landscape of alternative splicing in vertebrate species
    Nuno L Barbosa-Morais
    Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, Ontario, Canada
    Science 338:1587-93. 2012
    ..from vertebrate species spanning ~350 million years of evolution, we observed significant differences in alternative splicing complexity between vertebrate lineages, with the highest complexity in primates...
  10. pmc The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation
    Vidisha Tripathi
    Department of Cell and Developmental Biology, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Mol Cell 39:925-38. 2010
    b>Alternative splicing (AS) of pre-mRNA is utilized by higher eukaryotes to achieve increased transcriptome and proteomic complexity...
  11. pmc Analysis and design of RNA sequencing experiments for identifying isoform regulation
    Yarden Katz
    Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology MIT, Cambridge, Massachusetts, USA
    Nat Methods 7:1009-15. 2010
    Through alternative splicing, most human genes express multiple isoforms that often differ in function...
  12. pmc RNA and disease
    Thomas A Cooper
    Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
    Cell 136:777-93. 2009
    ..b>Alternative splicing provides cells with an exquisite capacity to fine-tune their transcriptome and proteome in response to cues...
  13. ncbi Alternative splicing: a pivotal step between eukaryotic transcription and translation
    Alberto R Kornblihtt
    Departamento de Fisiologia, Biología Molecular y Celular e Instituto de Fisiología, Biología Molecular y Neurociencias, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EHA Buenos Aires, Argentina
    Nat Rev Mol Cell Biol 14:153-65. 2013
    b>Alternative splicing was discovered simultaneously with splicing over three decades ago...
  14. ncbi The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
    Heather R Christofk
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 452:230-3. 2008
    ..These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo...
  15. pmc Genome-wide mapping of alternative splicing in Arabidopsis thaliana
    Sergei A Filichkin
    Department of Botany and Plant Pathology and Center for Genome Research and Biocomputing, Oregon State University, Corvallis, Oregon 97331, USA
    Genome Res 20:45-58. 2010
    b>Alternative splicing can enhance transcriptome plasticity and proteome diversity...
  16. pmc Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches
    Mo Chen
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nat Rev Mol Cell Biol 10:741-54. 2009
    b>Alternative splicing of mRNA precursors provides an important means of genetic control and is a crucial step in the expression of most genes...
  17. pmc MapSplice: accurate mapping of RNA-seq reads for splice junction discovery
    Kai Wang
    Department of Computer Science, University of Kentucky, Lexington, KY 40506, USA
    Nucleic Acids Res 38:e178. 2010
    ..Splice junctions derived from eight breast cancer RNA-seq datasets recapitulated the extensiveness of alternative splicing on a global level as well as the differences between molecular subtypes of breast cancer...
  18. pmc Functional consequences of developmentally regulated alternative splicing
    Auinash Kalsotra
    Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA
    Nat Rev Genet 12:715-29. 2011
    ..of metazoan transcriptomes have revealed an unexpected level of mRNA diversity that is generated by alternative splicing. Recently, regulatory networks have been identified through which splicing promotes dynamic remodelling of ..
  19. pmc Transcriptome survey reveals increased complexity of the alternative splicing landscape in Arabidopsis
    Yamile Márquez
    Max F Perutz Laboratories, Medical University of Vienna, Vienna, Austria
    Genome Res 22:1184-95. 2012
    b>Alternative splicing (AS) is a key regulatory mechanism that contributes to transcriptome and proteome diversity...
  20. pmc Regulation of alternative splicing by histone modifications
    Reini F Luco
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Science 327:996-1000. 2010
    b>Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. We demonstrated a direct role for histone modifications in alternative splicing...
  21. ncbi Frequent pathway mutations of splicing machinery in myelodysplasia
    Kenichi Yoshida
    Cancer Genomics Project, Graduate School of Medicine, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Nature 478:64-9. 2011
    ..Our results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia...
  22. pmc Improving the Arabidopsis genome annotation using maximal transcript alignment assemblies
    Brian J Haas
    The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA
    Nucleic Acids Res 31:5654-66. 2003
    ..4.0). The alignment assemblies permitted the automated modeling of several novel genes and >1000 alternative splicing variations as well as updates (including UTR annotations) to nearly half of the approximately 27 000 ..
  23. pmc Characterizing the RNA targets and position-dependent splicing regulation by TDP-43
    James R Tollervey
    Medical Research Council MRC Laboratory of Molecular Biology, Cambridge, UK
    Nat Neurosci 14:452-8. 2011
    ..We also found that binding of TDP-43 to pre-mRNAs influenced alternative splicing in a similar position-dependent manner to Nova proteins...
  24. pmc Epigenetics in alternative pre-mRNA splicing
    Reini F Luco
    National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 144:16-26. 2011
    b>Alternative splicing plays critical roles in differentiation, development, and disease and is a major source for protein diversity in higher eukaryotes...
  25. pmc Regulated functional alternative splicing in Drosophila
    Julian P Venables
    Universite Montpellier 2, UMR 5535, Institut de Genetique Moleculaire de Montpellier, CNRS, 1919 Route de Mende, 34293 Montpellier Cedex 05, France
    Nucleic Acids Res 40:1-10. 2012
    b>Alternative splicing expands the coding capacity of metazoan genes, and it was largely genetic studies in the fruit-fly Drosophila melanogaster that established the principle that regulated alternative splicing results in tissue- and ..
  26. pmc Deep RNA sequencing at single base-pair resolution reveals high complexity of the rice transcriptome
    Guojie Zhang
    Beijing Genomics Institute at Shenzhen, Shenzhen 518000, China
    Genome Res 20:646-54. 2010
    ..An analysis of alternative splicing in the rice transcriptome revealed that alternative cis-splicing occurred in approximately 33% of all rice ..
  27. ncbi Tissue-specific alternative splicing remodels protein-protein interaction networks
    Jonathan D Ellis
    Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada
    Mol Cell 46:884-92. 2012
    b>Alternative splicing plays a key role in the expansion of proteomic and regulatory complexity, yet the functions of the vast majority of differentially spliced exons are not known...
  28. ncbi TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity
    Antonella Caputo
    Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova 16148, Italy
    Science 322:590-4. 2008
    ....
  29. pmc The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing
    Eugene V Makeyev
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Mol Cell 27:435-48. 2007
    ..These events culminate in the transition from non-NS to NS-specific alternative splicing patterns...
  30. ncbi Deciphering the splicing code
    Yoseph Barash
    Biomedical Engineering, Department of Electrical and Computer Engineering, University of Toronto, 10 King s College Road, Toronto M5S 3G4, Canada
    Nature 465:53-9. 2010
    b>Alternative splicing has a crucial role in the generation of biological complexity, and its misregulation is often involved in human disease...
  31. pmc Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells
    Christine Mayr
    Howard Hughes Medical Institute, USA
    Cell 138:673-84. 2009
    ..The high incidence of APA in cancer cells, with consequent loss of 3'UTR repressive elements, suggests a pervasive role for APA in oncogene activation without genetic alteration...
  32. ncbi Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17
    M Hutton
    Mayo Clinic Jacksonville, Florida 32224, USA
    Nature 393:702-5. 1998
    ..mutations all destabilize a potential stem-loop structure which is probably involved in regulating the alternative splicing of exon10...
  33. ncbi Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy
    Charlotte Fugier
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U964, Centre National de la Recherche Scientifique UMR7104, University of Strasbourg, Illkirch, France
    Nat Med 17:720-5. 2011
    ..sequester the splicing regulator Muscleblind-like-1 (MBNL1), resulting in specific misregulation of the alternative splicing of other pre-mRNAs...
  34. pmc Muscleblind-like 2-mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy
    Konstantinos Charizanis
    Department of Molecular Genetics and Microbiology and the Center for NeuroGenetics, University of Florida, College of Medicine, Gainesville, FL 32610, USA
    Neuron 75:437-50. 2012
    ..Importantly, the majority of the Mbnl2-regulated exons examined were similarly misregulated in DM. We propose that major pathological features of the DM brain result from disruption of the MBNL2-mediated developmental splicing program...
  35. pmc Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged
    Charles J David
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Genes Dev 24:2343-64. 2010
    b>Alternative splicing of mRNA precursors is a nearly ubiquitous and extremely flexible point of gene control in humans...
  36. pmc RNA processing and its regulation: global insights into biological networks
    Donny D Licatalosi
    Howard Hughes Medical Institute, Laboratory of Molecular Neuro Oncology, The Rockefeller University, New York, New York 10021, USA
    Nat Rev Genet 11:75-87. 2010
    ..are revealing increasingly complete descriptions of RNA regulation and complexity; for example, through alternative splicing, alternative polyadenylation and RNA editing...
  37. ncbi Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays
    S A Bustin
    Academic Department of Surgery, St Bartholomew s and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London E1 1BB, UK
    J Mol Endocrinol 25:169-93. 2000
    ..It illustrates the usefulness of these assays by demonstrating the significantly different levels of transcription between individuals of the housekeeping gene family, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH)...
  38. ncbi A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome
    Marc Sultan
    Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany
    Science 321:956-60. 2008
    ..A global survey of messenger RNA splicing events identified 94,241 splice junctions (4096 of which were previously unidentified) and showed that exon skipping is the most prevalent form of alternative splicing.
  39. pmc Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping
    Yuanchao Xue
    Wuhan University, Hubei, China
    Mol Cell 36:996-1006. 2009
    Recent transcriptome analysis indicates that > 90% of human genes undergo alternative splicing, underscoring the contribution of differential RNA processing to diverse proteomes in higher eukaryotic cells...
  40. pmc Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing
    Madapura M Pradeepa
    MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    PLoS Genet 8:e1002717. 2012
    Increasing evidence suggests that chromatin modifications have important roles in modulating constitutive or alternative splicing. Here we demonstrate that the PWWP domain of the chromatin-associated protein Psip1/Ledgf can specifically ..
  41. ncbi Cryptic peroxisomal targeting via alternative splicing and stop codon read-through in fungi
    Johannes Freitag
    Department of Biology, Philipps University Marburg, Karl von Frisch Strasse 8, D 35032 Marburg, Germany
    Nature 485:522-5. 2012
    ..plant pathogen Ustilago maydis, peroxisomal targeting of Pgk1 results from ribosomal read-through, whereas alternative splicing generates the PTS1 of Gapdh...
  42. pmc Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins
    Stephanie C Huelga
    Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA
    Cell Rep 1:167-78. 2012
    ..Our findings define an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells...
  43. pmc HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer
    Charles J David
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Nature 463:364-8. 2010
    ..These two isoforms result from mutually exclusive alternative splicing of the PKM pre-mRNA, reflecting inclusion of either exon 9 (PKM1) or exon 10 (PKM2)...
  44. pmc iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution
    Julian König
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 17:909-15. 2010
    ..Integration of transcriptome-wide iCLIP data and alternative splicing profiles into an 'RNA map' indicates how the positioning of hnRNP particles determines their effect on the ..
  45. ncbi CLIP identifies Nova-regulated RNA networks in the brain
    Jernej Ule
    Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA
    Science 302:1212-5. 2003
    ..Thus, CLIP reveals that Nova coordinately regulates a biologically coherent set of RNAs encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in POMA...
  46. pmc Alternative splicing in plants--coming of age
    Naeem H Syed
    Division of Plant Sciences, University of Dundee at the James Hutton Institute, Invergowrie, Dundee DD2 5DA, Scotland, UK
    Trends Plant Sci 17:616-23. 2012
    More than 60% of intron-containing genes undergo alternative splicing (AS) in plants. This number will increase when AS in different tissues, developmental stages, and environmental conditions are explored...
  47. pmc Aberrant alternative splicing and extracellular matrix gene expression in mouse models of myotonic dystrophy
    Hongqing Du
    RNA Center, Department of Molecular, Cell and Developmental Biology, Sinsheimer Labs, University of California, Santa Cruz, California, USA
    Nat Struct Mol Biol 17:187-93. 2010
    ..These findings reveal unanticipated similarities between DM1 and other muscular dystrophies...
  48. pmc Position-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions
    Shinsuke Ishigaki
    Department of Neurology, Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Sci Rep 2:529. 2012
    FUS is an RNA-binding protein that regulates transcription, alternative splicing, and mRNA transport. Aberrations of FUS are causally associated with familial and sporadic ALS/FTLD...
  49. pmc Sex-specific and lineage-specific alternative splicing in primates
    Ran Blekhman
    Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA
    Genome Res 20:180-9. 2010
    ..Our data also suggest that while alternative splicing is tightly regulated within and between species, sex-specific and lineage-specific changes in the ..
  50. pmc An ESRP-regulated splicing programme is abrogated during the epithelial-mesenchymal transition
    Claude C Warzecha
    Renal Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    EMBO J 29:3286-300. 2010
    b>Alternative splicing achieves coordinated changes in post-transcriptional gene expression programmes through the activities of diverse RNA-binding proteins...
  51. pmc Statistical significance for genomewide studies
    John D Storey
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 100:9440-5. 2003
    ..Our approach avoids a flood of false positive results, while offering a more liberal criterion than what has been used in genome scans for linkage...
  52. ncbi Alternative splicing and evolution: diversification, exon definition and function
    Hadas Keren
    Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel
    Nat Rev Genet 11:345-55. 2010
    Over the past decade, it has been shown that alternative splicing (AS) is a major mechanism for the enhancement of transcriptome and proteome diversity, particularly in mammals...
  53. pmc "Cotranscriptionality": the transcription elongation complex as a nexus for nuclear transactions
    Roberto Perales
    Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, UCHSC, MS8101, P O Box 6511, Aurora CO, 80045, USA
    Mol Cell 36:178-91. 2009
    ..From this perspective, TECs can be viewed as potent "community organizers" within the nucleus...
  54. ncbi An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers
    Philip J Smith
    Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA
    Hum Mol Genet 15:2490-508. 2006
    ..Finally, we have derived an increased specificity score matrix that incorporates information from both of our SF2/ASF-specific matrices and that accurately predicts the exon-skipping phenotypes of deleterious point mutations...
  55. ncbi Aberrant and alternative splicing in cancer
    Julian P Venables
    University of Newcastle upon Tyne, Institute of Human Genetics, International Centre for Life, Central Parkway, Newcastle upon Tyne, United Kingdom
    Cancer Res 64:7647-54. 2004
    ..Also, many studies over the last 20 years have reported cancer-specific alternative splicing in the absence of genomic mutations...
  56. pmc Survey of the transcriptome of Aspergillus oryzae via massively parallel mRNA sequencing
    Bin Wang
    School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, China
    Nucleic Acids Res 38:5075-87. 2010
    ..oryzae and found a large number of genes undergoing alternative splicing. Many genes and pathways that might be involved in higher levels of protein production in solid-state ..
  57. ncbi Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy
    Xiaoyan Lin
    Department of Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA
    Hum Mol Genet 15:2087-97. 2006
    In myotonic dystrophy (DM), expression of RNA containing expanded CUG or CCUG repeats leads to misregulated alternative splicing of pre-mRNA...
  58. pmc CD44 splice isoform switching in human and mouse epithelium is essential for epithelial-mesenchymal transition and breast cancer progression
    Rhonda L Brown
    Department of Medicine, Division of Hematology Oncology, Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60614, USA
    J Clin Invest 121:1064-74. 2011
    ..Here we show that a switch in CD44 alternative splicing is required for EMT...
  59. pmc MATS: a Bayesian framework for flexible detection of differential alternative splicing from RNA-Seq data
    Shihao Shen
    Department of Biostatistics, University of Iowa, Iowa City, IA 52242, USA
    Nucleic Acids Res 40:e61. 2012
    Ultra-deep RNA sequencing has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We develop MATS (multivariate analysis of transcript splicing), a bayesian statistical framework for flexible hypothesis ..
  60. pmc Spliced leader trapping reveals widespread alternative splicing patterns in the highly dynamic transcriptome of Trypanosoma brucei
    Daniel Nilsson
    Institute of Cell Biology, University of Bern, Bern, Switzerland
    PLoS Pathog 6:e1001037. 2010
    ..Furthermore, we discovered more than 2500 alternative splicing events, many of which appear to be stage-regulated...
  61. pmc Prediction of alternative isoforms from exon expression levels in RNA-Seq experiments
    Hugues Richard
    Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Ihnestr 73, 14195 Berlin, Germany
    Nucleic Acids Res 38:e112. 2010
    b>Alternative splicing, polyadenylation of pre-messenger RNA molecules and differential promoter usage can produce a variety of transcript isoforms whose respective expression levels are regulated in time and space, thus contributing ..
  62. ncbi An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming
    Mathieu Gabut
    Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada
    Cell 147:132-46. 2011
    b>Alternative splicing (AS) is a key process underlying the expansion of proteomic diversity and the regulation of gene expression...
  63. ncbi Genome-wide analysis of transcript isoform variation in humans
    Tony Kwan
    Department of Human Genetics, McGill University, 740 Dr Penfield, Room 7210, Montreal, Quebec H3A 1A4, Canada
    Nat Genet 40:225-31. 2008
    ..This extra layer of molecular diversity may account for natural phenotypic variation and disease susceptibility...
  64. pmc HITS-CLIP yields genome-wide insights into brain alternative RNA processing
    Donny D Licatalosi
    Laboratory of Molecular Neuro Oncology and Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 456:464-9. 2008
    ..footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo...
  65. pmc An alternative splicing network links cell-cycle control to apoptosis
    Michael J Moore
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 142:625-36. 2010
    b>Alternative splicing is a vast source of biological regulation and diversity that is misregulated in cancer and other diseases...
  66. pmc Noisy splicing drives mRNA isoform diversity in human cells
    Joseph K Pickrell
    Department of Human Genetics, The University of Chicago, Chicago, Illinois, United States of America
    PLoS Genet 6:e1001236. 2010
    While the majority of multiexonic human genes show some evidence of alternative splicing, it is unclear what fraction of observed splice forms is functionally relevant...
  67. pmc Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB
    Miriam Llorian
    Department of Biochemistry, University of Cambridge, Cambridge, UK
    Nat Struct Mol Biol 17:1114-23. 2010
    ..Our results show that PTB, an archetypal splicing repressor, has variable splicing activity that predictably depends upon its binding location with respect to target exons...
  68. ncbi Genome-wide analyses of alternative splicing in plants: opportunities and challenges
    W Brad Barbazuk
    Donald Danforth Plant Science Center, St Louis, Missouri 63132, USA
    Genome Res 18:1381-92. 2008
    b>Alternative splicing (AS) creates multiple mRNA transcripts from a single gene. While AS is known to contribute to gene regulation and proteome diversity in animals, the study of its importance in plants is in its early stages...
  69. pmc Nucleosomes are well positioned in exons and carry characteristic histone modifications
    Robin Andersson
    The Linnaeus Centre for Bioinformatics, Uppsala University, Sweden
    Genome Res 19:1732-41. 2009
    ..Thus, exons are not only characterized by their coding capacity, but also by their nucleosome organization, which seems evolutionarily conserved since it is present in both primates and nematodes...
  70. pmc MBNL proteins repress ES-cell-specific alternative splicing and reprogramming
    Hong Han
    Banting and Best Department of Medical Research and Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada
    Nature 498:241-5. 2013
    ..b>Alternative splicing represents a widely acting mode of gene regulation, yet its role in regulating ES-cell pluripotency and ..
  71. pmc Genome-wide association between DNA methylation and alternative splicing in an invertebrate
    Kevin Flores
    School of Life Sciences, Arizona State University, PO Box 874501, 85287, Tempe, AZ, USA
    BMC Genomics 13:480. 2012
    ..data for one gene in each species to demonstrate that exon-specific DNA methylation may be associated with alternative splicing events...
  72. pmc RNA interference knockdown of DNA methyl-transferase 3 affects gene alternative splicing in the honey bee
    Hongmei Li-Byarlay
    Department of Entomology, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Proc Natl Acad Sci U S A 110:12750-5. 2013
    ..It has been postulated that regulation of alternative splicing of transcripts was an original function of DNA methylation, but a direct experimental test of the effect of ..
  73. ncbi Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function
    Olaf Isken
    Department of Biochemistry and Biophysics, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA
    Genes Dev 21:1833-56. 2007
    ..Along with other types of quality control that occur during the complex processes of mRNA biogenesis, these mRNA surveillance mechanisms help to ensure the integrity of protein-encoding gene expression...
  74. pmc Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain
    Boris Rogelj
    Centre for Neurodegeneration Research, King s College London, Institute of Psychiatry, De Crespigny Park, London, UK
    Sci Rep 2:603. 2012
    ..Analysis of FUS(-/-) brain demonstrated a role for FUS in alternative splicing, with increased crosslinking of FUS in introns around the repressed exons...
  75. ncbi Argonaute proteins couple chromatin silencing to alternative splicing
    Maya Ameyar-Zazoua
    Universite Paris Sud, Laboratoire Epigénétique et Cancer, Formation de Recherche en Evolution, Gif sur Yvette, France
    Nat Struct Mol Biol 19:998-1004. 2012
    ..AGO2 facilitate spliceosome recruitment and modulate RNA polymerase II elongation rate, thereby affecting alternative splicing. Proper AGO1 and AGO2 recruitment to CD44 transcribed regions required the endonuclease Dicer and the ..
  76. ncbi Function of alternative splicing
    Olga Kelemen
    Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA
    Gene 514:1-30. 2013
    Almost all polymerase II transcripts undergo alternative pre-mRNA splicing. Here, we review the functions of alternative splicing events that have been experimentally determined...
  77. ncbi Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9
    E Buratti
    International Center for Genetic Engineering and Biotechnology ICGEB 34012 Trieste, Italy
    J Biol Chem 276:36337-43. 2001
    ..In particular, the highly conserved Phe residues in the first RRM region play a key role in nucleic acid recognition...
  78. pmc Integrative modeling defines the Nova splicing-regulatory network and its combinatorial controls
    Chaolin Zhang
    Laboratory of Molecular Neuro Oncology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 329:439-43. 2010
    The control of RNA alternative splicing is critical for generating biological diversity. Despite emerging genome-wide technologies to study RNA complexity, reliable and comprehensive RNA-regulatory networks have not been defined...
  79. pmc Detection of splice junctions from paired-end RNA-seq data by SpliceMap
    Kin Fai Au
    Department of Statistics, Stanford University, Stanford, CA 94305, USA
    Nucleic Acids Res 38:4570-8. 2010
    b>Alternative splicing is a prevalent post-transcriptional process, which is not only important to normal cellular function but is also involved in human diseases...
  80. pmc An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells
    Gene W Yeo
    Crick Jacobs Center for Theoretical and Computational Biology, Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Struct Mol Biol 16:130-7. 2009
    ..These findings suggest that FOX2 functions as a critical regulator of a splicing network, and we further show that FOX2 is important for the survival of human embryonic stem cells...
  81. ncbi Alternative expression analysis by RNA sequencing
    Malachi Griffith
    Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, Canada
    Nat Methods 7:843-7. 2010
    ..Alternative expression annotation databases, source code, a data viewer and other resources to facilitate analysis are available at http://www.alexaplatform.org/alexa_seq/...
  82. pmc Alternative splicing and nonsense-mediated decay modulate expression of important regulatory genes in Arabidopsis
    Maria Kalyna
    Max F Perutz Laboratories, Medical University of Vienna, Dr Bohr Gasse 9 3, A 1030 Vienna, Austria
    Nucleic Acids Res 40:2454-69. 2012
    b>Alternative splicing (AS) coupled to nonsense-mediated decay (NMD) is a post-transcriptional mechanism for regulating gene expression...
  83. ncbi Two splice variants of the IDD14 transcription factor competitively form nonfunctional heterodimers which may regulate starch metabolism
    Pil Joon Seo
    Department of Chemistry, Seoul National University, Seoul 151 742, Korea
    Nat Commun 2:303. 2011
    b>Alternative splicing of primary gene transcripts provides eukaryotic cells, with a critical scheme for enriching transcriptome and proteome diversity...
  84. pmc A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart
    Auinash Kalsotra
    Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 105:20333-8. 2008
    From a large-scale screen using splicing microarrays and RT-PCR, we identified 63 alternative splicing (AS) events that are coordinated in 3 distinct temporal patterns during mouse heart development...
  85. pmc Degrade, move, regroup: signaling control of splicing proteins
    Florian Heyd
    Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6059, USA
    Trends Biochem Sci 36:397-404. 2011
    ..Recent studies now suggest notable trends in the mechanisms that link cellular stimuli to downstream alternative splicing events...
  86. pmc Comparison of transcriptomic landscapes of bovine embryos using RNA-Seq
    Wen Huang
    Department of Dairy Science, University of Wisconsin, Madison, WI 53706, USA
    BMC Genomics 11:711. 2010
    ..Although RNA-seq has been demonstrated in many organisms, no study has provided a comprehensive investigation of the bovine transcriptome using RNA-seq...
  87. ncbi 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease
    Sara Massone
    Oncology Biology and Genetics Department DOBiG, University of Genoa, Genoa, Italy
    Neurobiol Dis 41:308-17. 2011
    b>Alternative splicing is a central component of human brain complexity; nonetheless, its regulatory mechanisms are still largely unclear...
  88. pmc AltAnalyze and DomainGraph: analyzing and visualizing exon expression data
    Dorothea Emig
    Max Planck Institute for Informatics, 66123 Saarbrucken, Germany
    Nucleic Acids Res 38:W755-62. 2010
    b>Alternative splicing is an important mechanism for increasing protein diversity. However, its functional effects are largely unknown...
  89. pmc Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing
    Ignacio E Schor
    Departamento de Fisiologia, Biologia Molecular y Celular, IFIBYNE UBA Consejo Nacional de Investigaciones Científicas y Técnicas of Argentina, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina
    Proc Natl Acad Sci U S A 106:4325-30. 2009
    In search for physiological pathways affecting alternative splicing through its kinetic coupling with transcription, we found that membrane depolarization of neuronal cells triggers the skipping of exon 18 from the neural cell adhesion ..
  90. pmc Functional and evolutionary insights into human brain development through global transcriptome analysis
    Matthew B Johnson
    Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA
    Neuron 62:494-509. 2009
    ..These data reveal a large number of specific gene expression and alternative splicing patterns, as well as coexpression networks, associated with distinct regions and neurodevelopmental ..
  91. pmc ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing
    Claude C Warzecha
    Department of Medicine, Renal Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Cell 33:591-601. 2009
    ..These studies suggest that Epithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are coordinators of an epithelial cell-type-specific splicing program...
  92. ncbi A methyl transferase links the circadian clock to the regulation of alternative splicing
    Sabrina E Sanchez
    IFEVA, Facultad de Agronomia, UBA CONICET, C1417DSE Buenos Aires, Argentina
    Nature 468:112-6. 2010
    ..residues present in histones and Sm spliceosomal proteins, links the circadian clock to the control of alternative splicing in plants...
  93. pmc The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain
    Lauren T Gehman
    Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA
    Nat Genet 43:706-11. 2011
    The Rbfox family of RNA binding proteins regulates alternative splicing of many important neuronal transcripts, but its role in neuronal physiology is not clear...
  94. pmc Genome-wide analysis of alternative splicing in Caenorhabditis elegans
    Arun K Ramani
    Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, Ontario M5S 3E1, Canada
    Genome Res 21:342-8. 2011
    b>Alternative splicing (AS) plays a crucial role in the diversification of gene function and regulation...
  95. 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...
  96. ncbi Alternative splicing: global insights
    Martina Hallegger
    Department of Biochemistry, University of Cambridge, UK
    FEBS J 277:856-66. 2010
    ..splicing in 1977, it was quickly realized that splicing together of different combinations of splice sites--alternative splicing--allows individual genes to generate more than one mRNA isoform...
  97. ncbi Alternative splicing and disease
    Jamal Tazi
    University of Montpellier II, Institute of Molecular Genetics, Centre Nationale de Recherche Scientifique, 1919 Route de Mende, France
    Biochim Biophys Acta 1792:14-26. 2009
    Almost all protein-coding genes are spliced and their majority is alternatively spliced. Alternative splicing is a key element in eukaryotic gene expression that increases the coding capacity of the human genome and an increasing number ..
  98. pmc Epigenetic features are significantly associated with alternative splicing
    Yuanpeng Zhou
    State Key Laboratory of Genetic Engineering, Institute of Biostatistics, School of Life Science, Fudan University, Shanghai, China
    BMC Genomics 13:123. 2012
    While alternative splicing (AS) contributes greatly to protein diversities, the relationship between various types of AS and epigenetic factors remains largely unknown.
  99. pmc Genome-wide identification of alternative splice forms down-regulated by nonsense-mediated mRNA decay in Drosophila
    Kasper Daniel Hansen
    Division of Biostatistics, School of Public Health, University of California Berkeley, Berkeley, CA, USA
    PLoS Genet 5:e1000525. 2009
    ..Not all alternative splicing results in functional protein; it can also yield mRNA isoforms with premature stop codons that are degraded ..
  100. ncbi Polypyrimidine tract-binding protein homologues from Arabidopsis underlie regulatory circuits based on alternative splicing and downstream control
    Eva Stauffer
    Center for Plant Molecular Biology ZMBP, University of Tubingen, Auf der Morgenstelle 28, Tubingen, Germany
    Plant J 64:243-55. 2010
    b>Alternative splicing (AS) of precursor mRNAs is a widespread phenomenon in plants; however, many questions, especially regarding its regulation and functional implications, remain to be elucidated...
  101. ncbi More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation
    Reini F Luco
    National Cancer Institute, NIH, Bethesda, MD 20892, USA
    Curr Opin Genet Dev 21:366-72. 2011
    Large portions of the genome undergo alternative pre-mRNA splicing in often intricate patterns. Alternative splicing regulation requires extensive control mechanisms since errors can have deleterious consequences and may lead to ..

Research Grants78

  1. Pathogenesis of Myopathy in Models of Myotonic Dystrophy
    Charles Thornton; Fiscal Year: 2009
    ..nuclear foci ->sequestration of muscleblind [Mbnl] proteins in nuclear foci ->abnormal regulation of alternative splicing ->expression of inappropriate splice isoforms ->symptoms of DM...
  2. Alternative processing and antisense regulation of thyroid hormone receptor mRNA
    STEPHEN MUNROE; Fiscal Year: 2007
    ..The first specific aim is to characterize both cis-acting elements and trans-acting proteins that regulate alternative splicing specific to TRa2 mRNA...
  3. Mechanisms of Bronchial Myogenesis
    Lucia Schuger; Fiscal Year: 2005
    ..studies we found that heterogeneous ribonucleoprotein-H (hnRNP-H), an RNA-binding protein involved in alternative splicing, inhibits SM differentiation and bronchial myogenesis...
  4. Genetics and Haloperidol Response
    Robert J Hitzemann; Fiscal Year: 2012
    ..which genes (actually transcripts) within the QTL intervals show strong cis-regulation and strain specific alternative splicing and which genes show strong trans-regulation to the QTL intervals...
  5. BIOCHEMISTRY OF PRE-MRNA SPLICING
    Adrian R Krainer; Fiscal Year: 2010
    ..Many genes express multiple mRNA and protein isoforms by alternative splicing of their primary transcripts...
  6. REGULATION OF GENE EXPRESSION BY DIETARY FAT
    Lisa M Salati; Fiscal Year: 2012
    ..Because greater than 60% of genes undergo alternative splicing and many are also regulated by changes in splicing efficiency, these findings will have widespread ..
  7. Role of CD44 in experimental Multiple Sclerosis
    Mitzi Nagarkatti; Fiscal Year: 2013
    ..form of CD44 (CD44s) and upon activation, express certain unique variant isoforms of CD44 (CD44v) through alternative splicing. Specifically, we have shown that CD44 isoforms such as CD44v6/v7 play a critical role in the interaction ..
  8. Molecular Mechanisms of Parvovirus Gene Expression and Replication
    Jianming Qiu; Fiscal Year: 2013
    ..b>Alternative splicing of the B19V pre-mRNA, which is controlled by multiple splicing enhancers, plays a key role in regulating ..
  9. Novel Collagen II Alternative Transcripts and Mouse Skeletal Development
    Audrey McAlinden; Fiscal Year: 2010
    ..blocking a splice site in vitro, will prove to be a useful strategy to study any gene that is subject to alternative splicing. PUBLIC HEALTH RELEVANCE: This grant proposal will investigate the significance of novel type II collagen (..
  10. Gene Transcription in SLE
    George C Tsokos; Fiscal Year: 2012
    ..expression of CREM? in SLE T cells represents both increased promoter (newly characterized) activity and alternative splicing. It is hypothesized that cell membrane-initiated signaling processes lead to increased expression and ..
  11. Functional characterization of the Bronx waltzer deafness gene
    Botond Banfi; Fiscal Year: 2013
    ..with an SRRM4 transgene, 3) showed that SRRM4 is expressed in hair cells and neurons, 4) revealed that alternative splicing of several mRNAs is aberrant in the bv inner ear and that the affected mRNAs encode functionally related ..
  12. SMOOTH MUSCLE MYOSIN PHOSPHATASE SUBUNIT ISOFORMS
    Steven A Fisher; Fiscal Year: 2013
    ..We have shown that isoforms of MYPT1 generated by alternative splicing of a 31 nt exon (E23) are tissue-specific, developmentally regulated, evolutionarily conserved and modulate ..
  13. Testing Compounds that Increase SMN levels for Efficacy in Mouse Models of SMA
    Elliot J Androphy; Fiscal Year: 2010
    ..A nearly identical copy gene, SMN2, fails to protect from development of SMA because its mRNA undergoes alternative splicing that produces a truncated, unstable SMN protein...
  14. Regulation of Ovarian Cancer Multidrug Resistance by MAP Kinases
    Scott T Eblen; Fiscal Year: 2013
    ..Most importantly, phosphorylation of SPF45 on Ser222 by MAP kinases increases its alternative splicing activity...
  15. SPLICING OF MRNA PRECURSORS
    Michael R Green; Fiscal Year: 2013
    ..b>Alternative splicing is an important mechanism of gene regulation and is responsible for substantially increasing diversity of ..
  16. HEREDITARY DEFECTS IN HUMAN SODIUM CHANNELS
    Alfred L George; Fiscal Year: 2013
    ..Second, we will investigate whether alternative splicing influences the functional consequences of SCN1A mutations associated with divergent clinical phenotypes...
  17. Expression control in Drosophila splicing assembly factor RNP-4F
    JACK VAUGHN; Fiscal Year: 2010
    ..The region of interest undergoes alternative splicing to produce a second major mRNA isoform, and this process is developmentally regulated...
  18. Nuclear Function of Abl in DNA Damage Response
    Jean Y J Wang; Fiscal Year: 2012
    ..b>Alternative splicing has been shown to generate pro-death and anti-death protein isoforms from a single gene, underscoring the ..
  19. Modulation of Genes Responsible for Cilia Length by Exposure to Cigarette Smoke
    Ann E Tilley; Fiscal Year: 2013
    ..in a culture model;and (3) to evaluate the hypothesis that cigarette smoke exposure induces changes in alternative splicing of ODF2, resulting in dysfunctional cilia formation...
  20. Myosin 15:Genetics, Pathology and Therapeutic Potential
    Sally A Camper; Fiscal Year: 2013
    ..There are multiple isoforms of MYO15 that are generated by alternative splicing, including the presence or absence of a large proline-rich region N-terminal to the motor domain of MYO15...
  21. Cooperative lead development program for treatment of spinal muscular atrophy
    Elliot J Androphy; Fiscal Year: 2012
    ..A nearly identical copy gene, SMN2, fails to protect from development of SMA because its mRNA undergoes alternative splicing of exon 7. About 10% of SMN2 RNA transcripts include exon 7 and encode the same SMN protein as SMN1...
  22. The Role of Alternative Splicing Factor Sfrs10 in Neural Development
    Rahul N Kanadia; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Through alternative splicing a single gene can generate functionally diverse set of proteins...
  23. Alternative Splicing of the Insulin Receptor Gene
    NICHOLAS J WEBSTER; Fiscal Year: 2013
    ..The two variants arise from alternative splicing of exon 11...
  24. Innate and Adaptive Immune Mechanisms in Arthritis
    RICHARD J BUCALA; Fiscal Year: 2013
    ..Our working hypothesis is that MIF induces the alternative splicing of CD44, which regulates MIF-dependent responses and contributes to the immunopathogenesis of rheumatoid ..
  25. Functional Analysis of PAAN-AG5, the Baboon Counterpart of HLA-G5
    Daudi K Langat; Fiscal Year: 2010
    ..HLA-G and Paan-AG display remarkable similarity in the RNA processing, including alternative splicing of the mRNA, resulting in transcripts that encode membrane-anchored (HLA-G1-4 or Paan-AG1-4) and soluble ..
  26. FUNCTIONAL ANALYSIS OF NUCLEAR RECEPTOR VARIANTS
    Curtis J Omiecinski; Fiscal Year: 2013
    ..program included the discovery of novel forms of CAR, CAR2 and CAR3;receptors generated through the use of alternative splicing mechanisms that result in the insertion of 4- and 5- amino acids, respectively, within the receptors'..
  27. Mechanism Underlying Neurodegeneration Caused by Dysfunction of Pre-mRNA Splicing
    Yichang Jia; Fiscal Year: 2012
    ..Our transcriptome analysis revealed that only a subset of alternative splicing events, including splicing of small introns, is disrupted in the mutant cerebellum...
  28. Kinase/Phosphatase-mediated Mitochondrial Restructuring in Neuroprotection
    Stefan Strack; Fiscal Year: 2012
    ..explores regulation of the recently discovered Drp1 adaptor protein Mff (mitochondrial fission factor) by alternative splicing and phosphorylation...
  29. Statistical models to investigate long-distance QTL transcription regulation
    BARBARA ELIZABETH ENGELHARDT; Fiscal Year: 2011
    ..b>Alternative splicing has also been shown to modulate certain phenotypes;however, little is known about SNPs that regulate ..
  30. SMN Control of snRNP Biogenesis: Role in RNA Splicing and Motor Neuron Survival
    Livio Pellizzoni; Fiscal Year: 2013
    ..neurons as well as primary motor neurons from SMA mice, we will define the set of mRNAs whose expression or alternative splicing is selectively affected in motor neurons...
  31. EGFRvIII in Pancreatic Cancer
    Maneesh Jain; Fiscal Year: 2010
    ....
  32. Role of Splicing Factors in Breast Cancer
    OLGA ANCZUKOW-CAMARDA; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Cancer cells often display aberrant profiles of alternative splicing, leading to the production of protein isoforms that can increase cell proliferation, migration, and apoptotic resistance...
  33. The Functional Role of RBM45 in Gene Expression and Neurodegeneration
    Mahlon Collins; Fiscal Year: 2013
    ..We will next assess the contribution of RBM45 to the regulation of gene expression and alternative splicing. For these experiments, RBM45 will be depleted from cells via shRNA and the changes in gene expression and ..
  34. Role of Intronic Variants Affecting Splicing in Juvenile Myoclonic Epilepsy
    Debra J Wolgemuth; Fiscal Year: 2010
    ..Variation in the length of CA-repeats has been shown to affect alternative splicing events in other experimental models...
  35. Defining the messenger RNP code in the brain
    EUGENE WEI MING YEO; Fiscal Year: 2013
    ..These interactions result in the faithful execution of RNA processing events such as pre-mRNA alternative splicing, RNA stability and translational control...
  36. Alternative Splicing in Regulation of Cholesterol Synthesis and Uptake
    Marisa Wong Medina; Fiscal Year: 2013
    ..Recently, alternative splicing of the two most critical regulators of intracellular cholesterol, 3-hydroxy-3-methylglutaryl- coenzyme A ..
  37. Octopamine Neuroanatomy and Functioning in Fruit Fly Social Behavior
    KYLE LYNN GOBROGGE; Fiscal Year: 2013
    ..The fruitless gene displays sex- specific alternative splicing. Females make a truncated message that makes no protein...
  38. The Role of Caspase 9b Expression in NSCLC Survival/Chemotherapeutic Sensitivity
    Charles E Chalfant; Fiscal Year: 2013
    ..The expression of caspase 9b is regulated by alternative splicing via the inclusion or exclusion of a four exon cassette (exons 3, 4, 5, and 6)...
  39. MOLECULAR MANIPULATION TO ENHANCE ANTI-MYELOMA RESPONSE
    Nikhil C Munshi; Fiscal Year: 2013
    ..The proposed studies will identify the mechanism of immune suppression in myeloma, develop methods to improve immune function and develop peptide-based vaccination strategies to preclinical rational for their clinical application. ..
  40. Regulation of caspase 9 RNA splicing in NSCLC cancer
    Charles E Chalfant; Fiscal Year: 2013
    ..the grant application focuses on the cell signaling pathways regulating both hnRNP L function and the alternative splicing of caspase 9...
  41. GENE EXPRESSION EXON ARRAY BIOMARKERS TO DIAGNOSE SCHIZOPHRENIA
    Terry W Osborn; Fiscal Year: 2010
    ..The study would reveal variability of alternative splicing and confirm that we have the best set of biomarker genes for diagnostic product development...
  42. PGC-1alpha Proteins and the Control of Energy Metabolism
    Bruce M Spiegelman; Fiscal Year: 2013
    ..data for this proposal, we show that the PGC1a gene gives rise to several novel proteins in muscle via alternative splicing. The original PGC1a (now called PGC1a1) and a new shorter form (termed PGC1a4) are both highly induced ..
  43. Coloney Stimulating Factor 1 regulation and role in bone
    KARL LEONARD INSOGNA; Fiscal Year: 2010
    ..b>Alternative splicing of the CSF-1 gene results in production of soluble (sCSF1) and cell-surface (mCSF1) isoforms...
  44. Mechanisms of 5'UTR splicing of human surfactant protein (SP)-A1 and SP-A2
    Guirong Wang; Fiscal Year: 2011
    ..More than 70% of human genes express multiple mRNA variants through alternative splicing. About 20% of the variability from alternative splicing falls within the untranslated regions (5'UTR ..
  45. Disconnecting CR2/CD21 from Its C3d Ligand to Ameliorate Lupus
    VERNON MICHAEL HOLERS; Fiscal Year: 2013
    ..As opposed to humans, where unique genes encode these proteins, mouse CR2 and CR1 are derived through alternative splicing from a common gene designated Cr2...
  46. Macronutrient Regulation of Alternative Pre-mRNA Splicing
    Scot R Kimball; Fiscal Year: 2013
    ..applicant): We have recently discovered a novel and evolutionarily conserved homeostatic response wherein alternative splicing of the pre-mRNA encoding troponin T, a protein that affects muscle force production, is tightly regulated ..
  47. Role of Group 1B Phospholipase A2 on Diet-induced Metabolic Diseases
    David Y Hui; Fiscal Year: 2013
    ..G-to-A mutation alters an exon splicing enhancer sequence within exon 3 of the PLA2G1B gene, resulting in alternative splicing and deletion of the exon 3 domain to yield an inactive enzyme...
  48. Roles of MLL histone methyalses in estrogen mediated regulation of HDLR-SRB1
    Subhrangsu Mandal; Fiscal Year: 2010
    ..down of either MLL1 or MLL2 down regulated the estrogen mediated activation of SRB1 and also modulated the alternative splicing of SRB1 variants, suggesting their critical roles in these processes...
  49. Statistical models to investigate long-distance QTL transcription regulation
    BARBARA ELIZABETH ENGELHARDT; Fiscal Year: 2013
    ..b>Alternative splicing has also been shown to modulate certain phenotypes;however, little is known about SNPs that regulate ..
  50. Human Osteoprogenitor Control by Hepatocyte Growth Factor and Vitamin D
    Guy Howard; Fiscal Year: 2013
    ..involves two distinct promoters (an upstream promoter and an alternate promoter located in intron 3) and alternative splicing to generate mRNA...
  51. MECHANISMS OF ENHANCER DEPENDENT SPLICE SITE ACTIVATION
    Klemens J Hertel; Fiscal Year: 2013
    ..Current estimates indicate that over 90% of human genes undergo alternative splicing, thus greatly increasing the coding potential of our genome...
  52. Regulation of CD45 alternative splicing by HNRPLL
    Anjana Rao; Fiscal Year: 2013
    ..provided by applicant): The long-term goal of this project is to understand the mechanisms underlying CD45 alternative splicing and the role of CD45 splicing in lymphocyte and haematopoietic cell biology...
  53. Amino Acid Regulation of Alternative Splicing
    Michael S Kilberg; Fiscal Year: 2013
    ..the bZIP transcription factor ATF3, for which cellular stress induces multiple isoforms by pre-mRNA alternative splicing. Two of these isoforms, full- length ATF3 (ATF3-FL) and a form with a truncated leucine zipper, ATF3?Zip3, ..
  54. Spliceosome Mechanism Dissected at the Single Molecule Level
    Nils G Walter; Fiscal Year: 2013
    ..In humans, 94% of all pre-mRNAs undergo alternative splicing, which allows for the dynamic expression of various protein isoforms from a single gene through cell- and ..
  55. Functional Properties of Hair Cells and Spiral Ganglion Neurons
    Ebenezer N Yamoah; Fiscal Year: 2013
    ..We have identified 7 distinct spliced variants of Cav3.1 and predict that alternative splicing of mRNA produces distinct functional Cav3.1, which are specific to HCs...
  56. RNA editing-mediated modulation of serotonin 2C receptor protein expression
    RANDI JO ULBRICHT; Fiscal Year: 2011
    ..Furthermore, translation effects of MBII-52, a small nucleolar RNA (snoRNA) that can affect 5HT2C alternative splicing, will be investigated on both edited and non-edited 5HT2C mRNAs...
  57. Whole-genome analysis of direct Doublesex target genes
    MARK B VAN DOREN; Fiscal Year: 2012
    ..sexual development, such as those affecting DMRTs, and will provide a framework for understanding how the alternative splicing of transcription factors in general can lead to a diverse repertoire of downstream responses...
  58. MOLECULAR PATHOGENESIS OF MYOTONIC DYSTROPHY
    THOMAS ALEXANDER COOPER; Fiscal Year: 2013
    ..MBNL and CUGBP1 normally regulate pre-mRNA alternative splicing during development and the disruption of their functions in DM results in the splicing defects that have ..
  59. RNA Binding Protein CUGBP2 in Intestinal Epithelium
    Shrikant Anant; Fiscal Year: 2010
    ..In addition, CUGBP2 is regulated at the posttranscriptional level of alternative splicing resulting in the novel inclusion of one intron in the 5'untranslated region...
  60. Apoptosis pathways underlying adipogenesis
    Niketa A Patel; Fiscal Year: 2013
    ..In pursuit of this goal, our objective is to determine how alternative splicing of apoptotic genes govern the differentiation and maturation of pre-adipocytes...
  61. TORC2-dependent regulation of gluconeogensis
    MICHAEL DALE CONKRIGHT; Fiscal Year: 2012
    ..Our findings support the hypothesis that TORC2 controls gene expression and protein production via alternative splicing of cAMP target genes...
  62. Neuronal-Specific Splicing of CaV1.2 L-type Calcium Channels
    Kristin Webster; Fiscal Year: 2013
    ..This neuronal-specific function of CaV1.2 channels might arise from brain-specific alternative splicing. The N- terminus of CaV1...
  63. Mechanisms of Genotoxic Stress-regulated Gene Expression in Human Cells
    Mats Ljungman; Fiscal Year: 2013
    ..In Specific Aim #2, the effects of IR on alternative splicing will be interrogated...
  64. BAYESIAN APPROACHES TO MODEL SELECTION FOR SURVIVAL DATA
    Joseph G Ibrahim; Fiscal Year: 2013
    ..b>Alternative splicing of mRNA greatly expands the functional repertoire of many genes in the mammalian genome by including or ..
  65. Fragile X Mental Retardation Protein translation regulator function: interactions
    MIHAELA R MIHAILESCU; Fiscal Year: 2013
    ..through phosphorylation, due to the loss of the sites of phosphorylation from their sequence through alternative splicing. We will also determine if the production of the FMRP isoforms 2 and 3 is regulated through feedback ..
  66. HMG-CoA reductase alternative splicing and LDL response to statin
    Ronald M Krauss; Fiscal Year: 2010
    ..evidence in support of a novel pharmacogenetic mechanism contributing to this variation that involves alternative splicing of the mRNA for HMG-CoA reductase (HMGCR), the rate-limiting enzyme in cholesterol biosynthesis that is the ..
  67. Mechanisms Regulating Alternative pre-mRNA Splicing
    James Patton; Fiscal Year: 2005
    ..Further, 60% or more of human genes are subject to alternative splicing requiring that cells not only be able to accurately recognize the difference between introns and exons, but ..
  68. MECHANISM OF MIS-SPLICING IN MYOTONIC DYSTROPHY 1
    MUGE KUYUMCU MARTINEZ; Fiscal Year: 2007
    ..The pathogenesis of DM1 involves misregulation of alternative splicing resulting in expression of inappropriate protein isoforms causing specific symptoms...
  69. RNA Binding Proteins & Alternative Splicing
    Paula Grabowski; Fiscal Year: 2007
    ..b>Alternative splicing is a major driving force generating proteomic diversity in mammals, yet its mechanisms, regulatory networks,..
  70. Differential regulation of multiple transgenes for treatment of eye disease
    RICHARD J contact SAMULSKI; Fiscal Year: 2010
    ..a new type of regulation system without such drawbacks, we are exploring a novel regulation system based on alternative splicing. To date, we have developed minimal alternative splicing introns capable of regulating transgene expression...
  71. ALTERNATIVE SPLICING OF MOUSE AMELGENINS
    James Simmer; Fiscal Year: 1999
    ..In all species examined alternative splicing contributes to the diversity of amelogenins in the enamel matrix...
  72. REGULATION OF ALTERNATIVE RNA SPLICING IN A-TROPOMYOSIN
    David Wieczorek; Fiscal Year: 1992
    The objective of the proposed research is to enhance the understanding of mechanisms which regulate the alternative splicing process...
  73. MECHANISMS OF PREMRNA SPLICING
    THOMAS MANIATIS; Fiscal Year: 2001
    ..Experiments are proposed to address three aspects of RNA processing: 1. The regulation of alternative splicing. 2. The recognition and pairing of splice sites in constitutively spliced pre- mRNA. 3...
  74. ALTERNATIVE SPLICING OF THE CARDIAC TROPONIN T GENE
    Steven Lipshultz; Fiscal Year: 1990
    ..Other striated muscle TnT genes utilize alternative splicing of common and isotype specific exons to generate isoform diversity in response to developmental and tissue-..
  75. EXON-SPECIFIC FIBRONECTIN ISOFORMS AND CHONDROGENESIS
    NOREEN HICKOK; Fiscal Year: 2003
    ..Fibronectin isoform-changes result from mRNA alternative splicing events involving at least three exons in the fibronectin gene (IIIB, IIIA, and V)...
  76. CONTROL OF NEUROENDOCRINE GENE EXPRESSION
    STUART LEFF; Fiscal Year: 1992
    ..Four areas of research are proposed: 1) Regulation of alternative splicing: gene transfer studies...
  77. Global analysis of hnRNPLL-mediated alternative pre-mRNA splicing in lymphocytes.
    Shalini Oberdoerffer; Fiscal Year: 2009
    ..b>Alternative splicing is reciprocally linked to signal transduction pathways: the majority of transcripts modulated by ..
  78. Alternative splicing in the complex Drosophila dumpy gene
    Ross J MacIntyre; Fiscal Year: 2010
    ..This proposal concerns the role of alternative splicing in the differentiation and function of various extracellular matrices (ECMs) of epithelial cells during the ..