Nuclear matrix protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB.
EMBO J
; 34(5): 653-68, 2015 Mar 04.
Article
em En
| MEDLINE
| ID: mdl-25599992
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.
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MEDLINE
Assunto principal:
Proteínas de Ligação a RNA
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Processamento Alternativo
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Proteína de Ligação a Regiões Ricas em Polipirimidinas
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Proteínas Associadas à Matriz Nuclear
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Redes Reguladoras de Genes
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article