title: Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB.
abstract: Matrin3 is an RNA- and DNA-binding nuclear matrix protein found to be associated with neural and muscular degenerative diseases. A number of possible functions of Matrin3 have been suggested, but no widespread role in RNA metabolism has yet been clearly demonstrated. We identified Matrin3 by its interaction with the second RRM domain of the splicing regulator PTB. Using a combination of RNAi knockdown, transcriptome profiling and iCLIP, we find that Matrin3 is a regulator of hundreds of alternative splicing events, principally acting as a splicing repressor with only a small proportion of targeted events being co-regulated by PTB. In contrast to other splicing regulators, Matrin3 binds to an extended region within repressed exons and flanking introns with no sharply defined peaks. The identification of this clear molecular function of Matrin3 should help to clarify the molecular pathology of ALS and other diseases caused by mutations of Matrin3.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: Miguel B
authors.initials: MB
authors.lastname: Coelho
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK MRC-Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Attig
authors.affiliation: Computational Genomics, Universitat Pompeu Fabra, Barcelona, Spain Catalan Institute for Research and Advanced Studies (ICREA), Barcelona, Spain INIBIOMA CONICET-UNComahue, Bariloche, Argentina.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Bellora
authors.affiliation: MRC-Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: König
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, UK Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Martina
authors.initials: M
authors.lastname: Hallegger
authors.affiliation: MRC-Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Melis
authors.initials: M
authors.lastname: Kayikci
authors.affiliation: Computational Genomics, Universitat Pompeu Fabra, Barcelona, Spain Catalan Institute for Research and Advanced Studies (ICREA), Barcelona, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Eyras
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Jernej
authors.initials: J
authors.lastname: Ule
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, UK cwjs1@cam.ac.uk.
authors.forename: Christopher W J
authors.initials: CW
authors.lastname: Smith
mesh_terms: D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology*; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D046228:Microarray Analysis; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D038941:Polypyrimidine Tract-Binding Protein
keywords: Matrin3; PTB; alternative splicing