Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100
Name
15476286.2019.1667214.pdf
Description
Published version
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5.91 MB
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Unknown
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Author(s)
Capponi, Simona
Stöffler, Nadja
Irimia, Manuel
Van Schaik, Frederik MA
Ondik, Mercedes M
Biniossek, Martin L
Lehmann, Lisa
Mitschke, Julia
Vermunt, Marit W
Creyghton, Menno P
Date Issued
2020
Journal
RNA Biology
Publisher
Informa UK Limited
Version
Final published version
Abstract
© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Neuronal microexons represent the most highly conserved class of alternative splicing events and their timed expression shapes neuronal biology, including neuronal commitment and differentiation. The six-nt microexon 34ʹ is included in the neuronal form of TAF1 mRNA, which encodes the largest subunit of the basal transcription factor TFIID. In this study, we investigate the tissue distribution of TAF1-34ʹ mRNA and protein and the mechanism responsible for its neuronal-specific splicing. Using isoform-specific RNA probes and antibodies, we observe that canonical TAF1 and TAF1-34ʹ have different distributions in the brain, which distinguish proliferating from post-mitotic neurons. Knockdown and ectopic expression experiments demonstrate that the neuronal-specific splicing factor SRRM4/nSR100 promotes the inclusion of microexon 34ʹ into TAF1 mRNA, through the recognition of UGC sequences in the poly-pyrimidine tract upstream of the regulated microexon. These results show that SRRM4 regulates temporal and spatial expression of alternative TAF1 mRNAs to generate a neuronal-specific TFIID complex.
MIT Department
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1080/15476286.2019.1667214
