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EMBO J. 2015 Mar 4;34(5):653-68. doi: 10.15252/embj.201489852. Epub 2015 Jan 19.

Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB.

Author information

1
Department of Biochemistry, University of Cambridge, Cambridge, UK.
2
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK MRC-Laboratory of Molecular Biology, Cambridge, UK.
3
Computational Genomics, Universitat Pompeu Fabra, Barcelona, Spain Catalan Institute for Research and Advanced Studies (ICREA), Barcelona, Spain INIBIOMA CONICET-UNComahue, Bariloche, Argentina.
4
MRC-Laboratory of Molecular Biology, Cambridge, UK.
5
Department of Biochemistry, University of Cambridge, Cambridge, UK Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
6
Computational Genomics, Universitat Pompeu Fabra, Barcelona, Spain Catalan Institute for Research and Advanced Studies (ICREA), Barcelona, Spain.
7
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
8
Department of Biochemistry, University of Cambridge, Cambridge, UK cwjs1@cam.ac.uk.

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.

KEYWORDS:

Matrin3; PTB; alternative splicing

PMID:
25599992
PMCID:
PMC4365034
DOI:
10.15252/embj.201489852
[Indexed for MEDLINE]
Free PMC Article

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