THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
StandardStandard
Yn: iScience, Cyfrol 26, Rhif 1, 105784, 20.01.2023.
Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid
HarvardHarvard
APA
CBE
MLA
VancouverVancouver
Author
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 -