THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate
Allister, A. B.
Burbano de Lara, S.
El Bounkari, O.
Whetton, A. D.
Tran, D. D. H.
AffiliationDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover D-30623, Germany
MetadataShow full item record
AbstractTHOC5, 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.
CitationPolenkowski 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.
- Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus.
- Authors: Katahira J, Ishikawa H, Tsujimura K, Kurono S, Hieda M
- Issue date: 2019 Apr
- THOC5, a member of the mRNA export complex, contributes to processing of a subset of wingless/integrated (Wnt) target mRNAs and integrity of the gut epithelial barrier.
- Authors: Saran S, Tran DD, Klebba-Färber S, Moran-Losada P, Wiehlmann L, Koch A, Chopra H, Pabst O, Hoffmann A, Klopfleisch R, Tamura T
- Issue date: 2013 Nov 22
- THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo.
- Authors: Mancini A, Niemann-Seyde SC, Pankow R, El Bounkari O, Klebba-Färber S, Koch A, Jaworska E, Spooncer E, Gruber AD, Whetton AD, Tamura T
- Issue date: 2010 Jan 5
- Transcriptional regulation of immediate-early gene response by THOC5, a member of mRNA export complex, contributes to the M-CSF-induced macrophage differentiation.
- Authors: Tran DD, Saran S, Dittrich-Breiholz O, Williamson AJ, Klebba-Färber S, Koch A, Kracht M, Whetton AD, Tamura T
- Issue date: 2013 Oct 24
- Identification of mRNAs that are spliced but not exported to the cytoplasm in the absence of THOC5 in mouse embryo fibroblasts.
- Authors: Guria A, Tran DD, Ramachandran S, Koch A, El Bounkari O, Dutta P, Hauser H, Tamura T
- Issue date: 2011 Jun