WNK1 kinase and the termination factor PCF11 connect nuclear mRNA export with transcription

Genes Dev. 2017 Nov 1;31(21):2175-2185. doi: 10.1101/gad.303677.117. Epub 2017 Dec 1.

Abstract

Nuclear gene transcription is coordinated with transcript release from the chromatin template and messenger RNA (mRNA) export to the cytoplasm. Here we describe the role of nuclear-localized kinase WNK1 (with no lysine [K] 1) in the mammalian mRNA export pathway even though it was previously established as a critical regulator of ion homeostasis in the cytoplasm. Our data reveal that WNK1 phosphorylates the termination factor PCF11 on its RNA polymerase II (Pol II) C-terminal domain (CTD)-interacting domain (CID). Furthermore, phosphorylation of the PCF11 CID weakens its interaction with Pol II. We predict that WNK1 and the associated phosphorylation of the PCF11 CID act to promote transcript release from chromatin-associated Pol II. This in turn facilitates mRNA export to the cytoplasm.

Keywords: PCF11 CID; WNK1 kinase; mRNA export; transcription termination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • Cytoplasm / metabolism
  • HeLa Cells
  • Humans
  • Phosphorylation
  • Protein Domains
  • RNA Interference
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Transcription, Genetic*
  • WNK Lysine-Deficient Protein Kinase 1 / genetics
  • WNK Lysine-Deficient Protein Kinase 1 / metabolism*
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism*

Substances

  • Chromatin
  • Pcf11 protein, human
  • RNA, Messenger
  • mRNA Cleavage and Polyadenylation Factors
  • WNK Lysine-Deficient Protein Kinase 1
  • WNK1 protein, human
  • RNA Polymerase II