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THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate

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THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate. / Polenkowski, Mareike; Allister, Aldrige Bernardus; Burbano de Lara, Sebastian et al.
In: iScience, Vol. 26, No. 1, 105784, 20.01.2023.

Research output: Contribution to journal › Article › peer-review

HarvardHarvard

Polenkowski, M, Allister, AB, Burbano de Lara, S, Pierce, A, Geary, B, El Bounkari, O, Wiehlmann, L, Hoffmann, A, Whetton, AD, Tamura, T & Tran, DDH 2023, 'THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate', iScience, vol. 26, no. 1, 105784. https://doi.org/10.1016/j.isci.2022.105784

APA

Polenkowski, M., Allister, A. B., Burbano de Lara, S., Pierce, A., Geary, B., El Bounkari, O., Wiehlmann, L., Hoffmann, A., Whetton, A. D., Tamura, T., & Tran, D. D. H. (2023). THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate. iScience, 26(1), Article 105784. https://doi.org/10.1016/j.isci.2022.105784

CBE

Polenkowski M, Allister AB, Burbano de Lara S, Pierce A, Geary B, El Bounkari O, Wiehlmann L, Hoffmann A, Whetton AD, Tamura T, et al. 2023. THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate. iScience. 26(1):Article 105784. https://doi.org/10.1016/j.isci.2022.105784

MLA

Polenkowski, Mareike et al. "THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate". iScience. 2023. 26(1). https://doi.org/10.1016/j.isci.2022.105784

VancouverVancouver

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. doi: 10.1016/j.isci.2022.105784

Author

Polenkowski, Mareike ; Allister, Aldrige Bernardus ; Burbano de Lara, Sebastian et al. / THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate. In: iScience. 2023 ; Vol. 26, No. 1.

RIS

TY - JOUR

T1 - THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate

AU - Polenkowski, Mareike

AU - Allister, Aldrige Bernardus

AU - Burbano de Lara, Sebastian

AU - Pierce, Andrew

AU - Geary, Bethany

AU - El Bounkari, Omar

AU - Wiehlmann, Lutz

AU - Hoffmann, Andrea

AU - Whetton, Anthony D

AU - Tamura, Teruko

AU - Tran, Doan Duy Hai

N1 - © 2022 The Authors.

PY - 2023/1/20

Y1 - 2023/1/20

N2 - 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.

AB - 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.

U2 - 10.1016/j.isci.2022.105784

DO - 10.1016/j.isci.2022.105784

M3 - Article

C2 - 36590164

VL - 26

JO - iScience

JF - iScience

SN - 2589-0042

IS - 1

M1 - 105784

ER -