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THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate
Polenkowski, M. Allister, A. B. Burbano de Lara, S. Pierce, A. Geary, Bethany El Bounkari, O. Wiehlmann, L. Hoffmann, A. Whetton, A. D. Tamura, T.
Polenkowski, M.
Allister, A. B.
Burbano de Lara, S.
Pierce, A.
Geary, Bethany
El Bounkari, O.
Wiehlmann, L.
Hoffmann, A.
Whetton, A. D.
Tamura, T.
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Abstract
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.
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Date
2023
Publisher
Collections
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Type
Article
Citation
Polenkowski M, Allister AB, Burbano de Lara S, Pierce A, Geary B, El Bounkari O, et al. THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate. iScience. 2023 Jan 20;26(1):105784. PubMed PMID: 36590164. Pubmed Central PMCID: PMC9800341. Epub 2023/01/03. eng.