THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate
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- PIIS2589004222020570
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Dangosydd eitem ddigidol (DOI)
THOC5, a member of the THO complex, is essential for the 3'processing of some inducible genes, the export of a subset of mRNAs and stem cell survival. Here we show that THOC5 depletion results in altered 3'cleavage of >50% of mRNAs and changes in RNA polymerase II binding across genes. THOC5 is recruited close to high-density polymerase II sites, suggesting that THOC5 is involved in transcriptional elongation. Indeed, measurement of elongation rates in vivo demonstrated decreased rates in THOC5-depleted cells. Furthermore, THOC5 is preferentially recruited to its target genes in slow polymerase II cells compared with fast polymerase II cells. Importantly chromatin-associated THOC5 interacts with CDK12 (a modulator of transcription elongation) and RNA helicases DDX5, DDX17, and THOC6 only in slow polymerase II cells. The CDK12/THOC5 interaction promotes CDK12 recruitment to R-loops in a THOC6-dependent manner. These data demonstrate a novel function of THOC5 in transcription elongation.
Iaith wreiddiol | Saesneg |
---|---|
Rhif yr erthygl | 105784 |
Cyfnodolyn | iScience |
Cyfrol | 26 |
Rhif y cyfnodolyn | 1 |
Dynodwyr Gwrthrych Digidol (DOIs) | |
Statws | Cyhoeddwyd - 20 Ion 2023 |
Cyhoeddwyd yn allanol | Ie |