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Multilayered Control of Alternative Splicing Regulatory Networks by Transcription Factors

dechang 添加于 2017-2-14 09:35 | 1862 次阅读 | 0 个评论

作者
Han H, Braunschweig U, Gonatopoulos-Pournatzis T, Weatheritt RJ, Hirsch CL, Ha KCH, Radovani E, Nabeel-Shah S, Sterne-Weiler T, Wang J, O\'Hanlon D, Pan Q, Ray D, Zheng H, Vizeacoumar F, Datti A, Magomedova L, Cummins CL, Hughes TR, Greenblatt JF, Wrana JL, Moffat J, Blencowe BJ
摘要
Networks of coordinated alternative splicing (AS) events play critical roles in development and disease. However, a comprehensive knowledge of the factors that regulate these networks is lacking. We describe a high-throughput system for systematically linking trans-acting factors to endogenous RNA regulatory events. Using this system, we identify hundreds of factors associated with diverse regulatory layers that positively or negatively control AS events linked to cell fate. Remarkably, more than one-third of the regulators are transcription factors. Further analyses of the zinc finger protein Zfp871 and BTB/POZ domain transcription factor Nacc1, which regulate neural and stem cell AS programs, respectively, reveal roles in controlling the expression of specific splicing regulators. Surprisingly, these proteins also appear to regulate target AS programs via binding RNA. Our results thus uncover a large \"missing cache\" of splicing regulators among annotated transcription factors, some of which dually regulate AS through direct and indirect mechanisms.
详细资料
- 关键词: RNA interference; SPAR-seq; alternative splicing; chromatin; embryonic stem cells; high-throughput screening; neuroblastoma cells; spliceosome; splicing factors; transcription factors
- 文献种类:期刊
- 期刊名称: Molecular Cell
- 期刊缩写: Mol Cell
- 期卷页: 2017年第65卷第3期 539-553.e7页
- 地址: Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: b.blencowe@utoronto.ca
- ISBN: 1097-2765
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