Capponi, SimonaStöffler, NadjaIrimia Martínez, ManuelVan Schaik, Frederik M.A.Ondik, Mercedes M.Biniossek, Martin L.Lehmann, LisaMitschke, JuliaVermunt, Marit W.Creygthon, Menno P.Graybiel, Ann M.Reinheckel, ThomasSchilling, OliverBlencowe, Benjamin J.Crittenden, Jill R.Timmers, Marc2020-04-282020-04-282020Capponi S, Stöffler N, Irimia M, Van Schaik FMA, Ondik MM, Biniossek ML et al. Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100. RNA Biol. 2020 Jan; 17(1): 62-74. DOI: 10.1080/15476286.2019.16672141547-6286http://hdl.handle.net/10230/44354Neuronal 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 34' 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 TAF1-34' 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 TAF1-34' 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 34' 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.application/pdfeng© 2019 Simona Capponi et al. Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any wayNeurologiainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1080/15476286.2019.1667214info:eu-repo/semantics/openAccess