Tyrosine phosphorylation of RNA polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells

Nicolas Descostes (1, 2, 3, 4) , Martin Heidemann (5) , Lionel Spinelli (3, 1, 2) , Roland Schüller (5) , Muhammad Ahmad Maqbool (3, 4, 1, 2) , Romain Fenouil (3, 1, 2) , Frederic Koch (3, 1, 2) , Charlène Innocenti (3, 1, 2) , Marta Gut (6) , Ivo Gut (6) , Dirk Eick (5) , Jean-Christophe Andrau (3, 4, 1, 2)

1 INSERM - Institut National de la Santé et de la Recherche Médicale
2 CNRS - Centre National de la Recherche Scientifique
3 CIML - Centre d'Immunologie de Marseille - Luminy
4 IGMM - Institut de Génétique Moléculaire de Montpellier
5 Helmholtz Zentrum München = German Research Center for Environmental Health
6 Centre Nacional D'Anàlisi Genómica

In mammals, the carboxy-terminal domain (CTD) of RNA polymerase (Pol) II consists of 52 conserved heptapeptide repeats containing the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Post-translational modifications of the CTD coordinate the transcription cycle and various steps of mRNA maturation. Here we describe Tyr1 phosphorylation (Tyr1P) as a hallmark of promoter (5′ associated) Pol II in mammalian cells, in contrast to what was described in yeast. Tyr1P is predominantly found in antisense orientation at promoters but is also specifically enriched at active enhancers. Mutation of Tyr1 to phenylalanine (Y1F) prevents the formation of the hyper-phosphorylated Pol IIO form, induces degradation of Pol II to the truncated Pol IIB form, and results in a lethal phenotype. Our results suggest that Tyr1P has evolved specialized and essential functions in higher eukaryotes associated with antisense promoter and enhancer transcription, and Pol II stability.

Domains: Life Sciences [q-bio]; Quantitative Methods [q-bio.QM]

Nicolas Descostes, Martin Heidemann, Lionel Spinelli, Roland Schüller, Muhammad Ahmad Maqbool, et al.. Tyrosine phosphorylation of RNA polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells. eLife, 2014, 3, ⟨10.7554/eLife.02105⟩. ⟨hal-01431911⟩