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Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB.
EMBO J. 2015 Mar 04; 34(5):653-68.EJ

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+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25599992

Citation

Coelho, Miguel B., et al. "Nuclear Matrix Protein Matrin3 Regulates Alternative Splicing and Forms Overlapping Regulatory Networks With PTB." The EMBO Journal, vol. 34, no. 5, 2015, pp. 653-68.
Coelho MB, Attig J, Bellora N, et al. Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB. EMBO J. 2015;34(5):653-68.
Coelho, M. B., Attig, J., Bellora, N., König, J., Hallegger, M., Kayikci, M., Eyras, E., Ule, J., & Smith, C. W. (2015). Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB. The EMBO Journal, 34(5), 653-68. https://doi.org/10.15252/embj.201489852
Coelho MB, et al. Nuclear Matrix Protein Matrin3 Regulates Alternative Splicing and Forms Overlapping Regulatory Networks With PTB. EMBO J. 2015 Mar 4;34(5):653-68. PubMed PMID: 25599992.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB. AU - Coelho,Miguel B, AU - Attig,Jan, AU - Bellora,Nicolás, AU - König,Julian, AU - Hallegger,Martina, AU - Kayikci,Melis, AU - Eyras,Eduardo, AU - Ule,Jernej, AU - Smith,Christopher W J, Y1 - 2015/01/19/ PY - 2015/1/21/entrez PY - 2015/1/21/pubmed PY - 2015/5/6/medline KW - Matrin3 KW - PTB KW - alternative splicing SP - 653 EP - 68 JF - The EMBO journal JO - EMBO J. VL - 34 IS - 5 N2 - 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. SN - 1460-2075 UR - https://www.unboundmedicine.com/medline/citation/25599992/Nuclear_matrix_protein_Matrin3_regulates_alternative_splicing_and_forms_overlapping_regulatory_networks_with_PTB_ L2 - https://doi.org/10.15252/embj.201489852 DB - PRIME DP - Unbound Medicine ER -