期刊
RNA BIOLOGY
卷 17, 期 1, 页码 62-74出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2019.1667214
关键词
Alternative mRNA splicing; microexons; neuronal transcription; neurogenesis; basal transcription factors; TAF1; X-linked Dystonia Parkinsonism
资金
- Collaborative Centre for X-linked Dystonia Parkinsonism
- James and Pat Poitras Research Fund
- Saks Kavanaugh Foundation
- Stichting Parkinson Fonds
- Deutsche Forschungsgemeinschaft [SFB850, SFB992, GR 1748/6-1, SCHI 871/8-1, SCHI 871/9-1, SCHI 871/11-1, INST 39/900-1, INST 39/766-3, Re1584/6-2]
- Excellence Initiative of the German Federal and State Governments [EXC 294, GSC-4]
- German-Israel Foundation [I-1444-201.2/2017]
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 34MODIFIER LETTER PRIME 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 TAF1-34MODIFIER LETTER PRIME 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 TAF1-34MODIFIER LETTER PRIME 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 34MODIFIER LETTER PRIME 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.
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