Nuclear Matrix Protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB
Coelho, Miguel B
The EMBO Journal
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Coelho, M. B., Attig, J., Bellora, N., König, J., Hallegger, M., Kayikci, M., Eyras, E., et al. (2015). Nuclear Matrix Protein Matrin3 regulates alternative splicing and forms overlapping regulatory networks with PTB. The EMBO Journal, 34 653-668. https://doi.org/10.15252/embj.201489852
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.
alternative splicing, Matrin3, PTB
We thank Nejc Haberman (UCL) for assisting in the generation of the splicing maps and preparation of the iCLIP data. This work was supported by Wellcome Trust programme grants to CWJS (077877 and 092900), and by grants to EE and NB BIO2011-23920 and RNAREG (CSD2009-00080) from the Spanish Government and by the Sandra Ibarra Foundation for Cancer (FSI2013). JA was supported by a Boehringer Ingelheim Fonds studentship.
Wellcome Trust (092900/Z/10/Z)
Wellcome Trust (077877/Z/05/Z)
External DOI: https://doi.org/10.15252/embj.201489852
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246892
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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