Tyrosine-1 of RNA Polymerase II CTD Controls Global Termination of Gene Transcription in Mammals.

Nilay Shah , Muhammad Ahmad Maqbool , Yousra Yahia , Amal Zine El Aabidine , Cyril Esnault (1) , Ignasi Forné , Tim-Michael Decker , David Martin , Roland Schüller , Stefan Krebs , Helmut Blum , Axel Imhof , Dirk Eick , Jean-Christophe Andrau (1)

1 IGMM - Institut de Génétique Moléculaire de Montpellier

The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is composed of a repetition of YSPTSPS heptads and functions as a loading platform for protein complexes that regulate transcription, splicing, and maturation of RNAs. Here, we studied mammalian CTD mutants to analyze the function of tyrosine1 residues in the transcription cycle. Mutation of 3/4 of the tyrosine residues (YFFF mutant) resulted in a massive read-through transcription phenotype in the antisense direction of promoters as well as in the 3' direction several hundred kilobases downstream of genes. The YFFF mutant shows reduced Pol II at promoter-proximal pause sites, a loss of interaction with the Mediator and Integrator complexes, and impaired recruitment of these complexes to chromatin. Consistent with these observations, Pol II loading at enhancers and maturation of snRNAs are altered in the YFFF context genome-wide. We conclude that tyrosine1 residues of the CTD control termination of transcription by Pol II.

Mots clés: CTD; RNA polymerase II; Tyrosine1; divergent transcription; promoter-proximal pausing; read-through transcription; transcription termination

Domaines: Sciences du Vivant [q-bio]

Nilay Shah, Muhammad Ahmad Maqbool, Yousra Yahia, Amal Zine El Aabidine, Cyril Esnault, et al.. Tyrosine-1 of RNA Polymerase II CTD Controls Global Termination of Gene Transcription in Mammals.. Molecular Cell, 2018, 69 (1), pp.48-61.e6. ⟨10.1016/j.molcel.2017.12.009⟩. ⟨hal-03022268⟩