CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription

Mol Cell. 2016 Mar 3;61(5):734-746. doi: 10.1016/j.molcel.2016.02.008.

Abstract

The creation of translation-competent mRNA is dependent on RNA polymerase II transcripts being modified by addition of the 7-methylguanosine (m7G) cap. The factors that mediate splicing, nuclear export, and translation initiation are recruited to the transcript via the cap. The cap structure is formed by several activities and completed by RNMT (RNA guanine-7 methyltransferase), which catalyzes N7 methylation of the cap guanosine. We report that CDK1-cyclin B1 phosphorylates the RNMT regulatory domain on T77 during G2/M phase of the cell cycle. RNMT T77 phosphorylation activates the enzyme both directly and indirectly by inhibiting interaction with KPNA2, an RNMT inhibitor. RNMT T77 phosphorylation results in elevated m7G cap methyltransferase activity at the beginning of G1 phase, coordinating mRNA capping with the burst of transcription that occurs following nuclear envelope reformation. RNMT T77 phosphorylation is required for the production of cohort of proteins, and inhibiting T77 phosphorylation reduces the cell proliferation rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CDC2 Protein Kinase
  • Cell Proliferation
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism*
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Enzyme Activation
  • G1 Phase*
  • G2 Phase
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • RNA Caps / genetics
  • RNA Caps / metabolism*
  • RNA Interference
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • S Phase
  • Signal Transduction
  • Time Factors
  • Transcription, Genetic*
  • Transfection
  • alpha Karyopherins / genetics
  • alpha Karyopherins / metabolism

Substances

  • CCNB1 protein, human
  • Cyclin B1
  • KPNA2 protein, human
  • RNA Caps
  • RNA, Messenger
  • alpha Karyopherins
  • Methyltransferases
  • mRNA (guanine(N7))-methyltransferase
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases