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Exon-Mediated Activation of Transcription Starts.
Cell ( IF 45.5 ) Pub Date : 2019-11-28 , DOI: 10.1016/j.cell.2019.11.002
Ana Fiszbein 1 , Keegan S Krick 1 , Bridget E Begg 1 , Christopher B Burge 1
Affiliation  

The processing of RNA transcripts from mammalian genes occurs in proximity to their transcription. Here, we describe a phenomenon affecting thousands of genes that we call exon-mediated activation of transcription starts (EMATS), in which the splicing of internal exons impacts promoter choice and the expression level of the gene. We observed that evolutionary gain of internal exons is associated with gain of new transcription start sites (TSSs) nearby and increased gene expression. Inhibiting exon splicing reduced transcription from nearby promoters, and creation of new spliced exons activated transcription from cryptic promoters. The strongest effects occurred for weak promoters located proximal and upstream of efficiently spliced exons. Together, our findings support a model in which splicing recruits transcription machinery locally to influence TSS choice and identify exon gain, loss, and regulatory change as major contributors to the evolution of alternative promoters and gene expression in mammals.

中文翻译:

外显子介导的转录激活开始。

来自哺乳动物基因的 RNA 转录物的加工发生在它们的转录附近。在这里,我们描述了一种影响数千个基因的现象,我们称之为外显子介导的转录启动激活 (EMATS),其中内部外显子的剪接影响启动子的选择和基因的表达水平。我们观察到内部外显子的进化增益与附近新转录起始位点 (TSS) 的增益和基因表达的增加有关。抑制外显子剪接会减少来自附近启动子的转录,而新剪接外显子的产生会激活来自神秘启动子的转录。位于有效剪接外显子近端和上游的弱启动子的作用最强。一起,
更新日期:2019-11-29
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