RNA polymerase II CTD is dispensable for transcription and required for termination in human cells.
Fiche publication
Date publication
juillet 2023
Journal
EMBO reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SEXTON Thomas
Tous les auteurs :
Yahia Y, Pigeot A, El Aabidine AZ, Shah N, Karasu N, Forné I, Krebs S, Blum H, Esnault C, Sexton T, Imhof A, Eick D, Andrau JC
Lien Pubmed
Résumé
The largest subunit of RNA polymerase (Pol) II harbors an evolutionarily conserved C-terminal domain (CTD), composed of heptapeptide repeats, central to the transcriptional process. Here, we analyze the transcriptional phenotypes of a CTD-Δ5 mutant that carries a large CTD truncation in human cells. Our data show that this mutant can transcribe genes in living cells but displays a pervasive phenotype with impaired termination, similar to but more severe than previously characterized mutations of CTD tyrosine residues. The CTD-Δ5 mutant does not interact with the Mediator and Integrator complexes involved in the activation of transcription and processing of RNAs. Examination of long-distance interactions and CTCF-binding patterns in CTD-Δ5 mutant cells reveals no changes in TAD domains or borders. Our data demonstrate that the CTD is largely dispensable for the act of transcription in living cells. We propose a model in which CTD-depleted Pol II has a lower entry rate onto DNA but becomes pervasive once engaged in transcription, resulting in a defect in termination.
Mots clés
Pol II interactome, RNA polymerase II (Pol II), carboxy-terminal domain (CTD), mammalian transcription, termination
Référence
EMBO Rep. 2023 07 10;:e56150