A Transcriptome-wide Antitermination Mechanism Sustaining Identity of Embryonic Stem Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jan 19

PMID 31953406

Citations 10

Authors

Yaroslav A Kainov

Eugene V Makeyev

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Regulation of alternative splicing and polyadenylation in neurons.

Lee S, Aubee J, Lai E Life Sci Alliance. 2023; 6(12).

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An 840 kb distant upstream enhancer is a crucial regulator of catecholamine-dependent expression of the Bdnf gene in astrocytes.

Avarlaid A, Esvald E, Koppel I, Parkman A, Zhuravskaya A, Makeyev E Glia. 2023; 72(1):90-110.

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U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3' end processing core factors.

Hu Z, Li M, Huo Z, Chen L, Liu S, Deng K J Mol Cell Biol. 2022; 14(8).

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Multi-omics approach reveals posttranscriptionally regulated genes are essential for human pluripotent stem cells.

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