A transcriptome-wide antitermination mechanism sustaining identity of embryonic stem cells.,Nature Communications

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A transcriptome-wide antitermination mechanism sustaining identity of embryonic stem cells.
Nature Communications ( IF 14.7 ) Pub Date : 2020-01-17 , DOI: 10.1038/s41467-019-14204-z
Yaroslav A Kainov ₁ , Eugene V Makeyev ₁

Affiliation

Eukaryotic gene expression relies on extensive crosstalk between transcription and RNA processing. Changes in this composite regulation network may provide an important means for shaping cell type-specific transcriptomes. Here we show that the RNA-associated protein Srrt/Ars2 sustains embryonic stem cell (ESC) identity by preventing premature termination of numerous transcripts at cryptic cleavage/polyadenylation sites in first introns. Srrt interacts with the nuclear cap-binding complex and facilitates recruitment of the spliceosome component U1 snRNP to cognate intronic positions. At least in some cases, U1 recruited in this manner inhibits downstream cleavage/polyadenylation events through a splicing-independent mechanism called telescripting. We further provide evidence that the naturally high expression of Srrt in ESCs offsets deleterious effects of retrotransposable sequences accumulating in its targets. Our work identifies Srrt as a molecular guardian of the pluripotent cell state.

中文翻译：

转录组范围的抗终止机制，维持胚胎干细胞的身份。

真核基因表达依赖于转录和RNA加工之间的广泛串扰。该复合调控网络的变化可能为塑造特定于细胞类型的转录组提供重要手段。在这里，我们显示RNA相关蛋白Srrt / Ars2通过防止在第一个内含子中的隐含裂解/聚腺苷酸化位点的许多转录物过早终止而维持了胚胎干细胞（ESC）的身份。Srrt与核帽结合复合物相互作用，并促进剪接体组件U1 snRNP募集到同源内含子位置。至少在某些情况下，以这种方式募集的U1通过称为剪接的非剪接独立机制抑制下游裂解/聚腺苷酸化事件。我们进一步提供证据，表明Srrt在ESC中的天然高表达抵消了在其靶标中积累的可逆转座序列的有害作用。我们的工作将Srrt鉴定为多能细胞状态的分子监护者。

更新日期：2020-01-17

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