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

Allbwn ymchwil: Cyfraniad at gyfnodolynErthygladolygiad gan gymheiriaid

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  • Mareike Polenkowski
    Hannover Medical School
  • Aldrige Bernardus Allister
    Hannover Medical School
  • Sebastian Burbano de Lara
    DKFZ-ZMBH Alliance German Cancer Research Center
  • Andrew Pierce
    Stem Cell and Leukemia Protoemics LaboratoryManchester University
  • Bethany Geary
    Manchester University
  • Omar El Bounkari
    Institute for Stroke and Dementia Research
  • Lutz Wiehlmann
    Pädiatrische Pneumologie Hannover Medical School
  • Andrea Hoffmann
    Hannover Medical School
  • Anthony D Whetton
    Manchester University
  • Teruko Tamura
    Institut für Zellbiochemie
  • Doan Duy Hai Tran
    Hannover Medical School

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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Rhif yr erthygl105784
CyfnodolyniScience
Cyfrol26
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Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - 20 Ion 2023
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