Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100
© 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....
| Main Authors: | , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Informa UK Limited
2021
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| Online Access: | https://hdl.handle.net/1721.1/136412 |
| _version_ | 1826194858464772096 |
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| author | 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 Graybiel, Ann M Reinheckel, Thomas Schilling, Oliver Blencowe, Benjamin J Crittenden, Jill R Timmers, H Th Marc |
| author2 | McGovern Institute for Brain Research at MIT |
| author_facet | McGovern Institute for Brain Research at MIT 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 Graybiel, Ann M Reinheckel, Thomas Schilling, Oliver Blencowe, Benjamin J Crittenden, Jill R Timmers, H Th Marc |
| author_sort | Capponi, Simona |
| collection | MIT |
| description | © 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. |
| first_indexed | 2024-09-23T10:03:17Z |
| format | Article |
| id | mit-1721.1/136412 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:03:17Z |
| publishDate | 2021 |
| publisher | Informa UK Limited |
| record_format | dspace |
| spelling | mit-1721.1/1364122023-02-16T19:31:55Z Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100 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 Graybiel, Ann M Reinheckel, Thomas Schilling, Oliver Blencowe, Benjamin J Crittenden, Jill R Timmers, H Th Marc McGovern Institute for Brain Research at MIT Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences © 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. 2021-10-27T20:35:14Z 2021-10-27T20:35:14Z 2020 2021-03-24T17:30:19Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136412 en 10.1080/15476286.2019.1667214 RNA Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/octet-stream Informa UK Limited Taylor & Francis |
| spellingShingle | 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 Graybiel, Ann M Reinheckel, Thomas Schilling, Oliver Blencowe, Benjamin J Crittenden, Jill R Timmers, H Th Marc Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100 |
| title | Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100 |
| title_full | Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100 |
| title_fullStr | Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100 |
| title_full_unstemmed | Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100 |
| title_short | Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100 |
| title_sort | neuronal specific microexon splicing of taf1 mrna is directly regulated by srrm4 nsr100 |
| url | https://hdl.handle.net/1721.1/136412 |
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