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.

Cited by papers we hold 8

• RNA-recognition motif in Matrin-3 mediates neurodegeneration through interaction with hnRNPM · 2020
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• Molecular and Cellular Mechanisms Affected in ALS · 2020
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• RNA Dysregulation in Amyotrophic Lateral Sclerosis · 2019
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• Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing · 2018
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• A Short Tandem Repeat-Enriched RNA Assembles a Nuclear Compartment to Control Alternative Splicing and Promote Cell Survival · 2018
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• Handshakes and Fights: The Regulatory Interplay of RNA-Binding Proteins · 2017
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• The RNA Splicing Response to DNA Damage · 2015
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• The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation · 2015
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