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

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

Author information

1
Centre for Gene Regulation and Expression/MRC Phosphorylation and Ubiquitylation, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
2
Division of Signal Transduction Therapy, University of Dundee, Dundee DD1 5EH, UK.
3
Centre for Gene Regulation and Expression/MRC Phosphorylation and Ubiquitylation, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Electronic address: v.h.cowling@dundee.ac.uk.

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.

PMID:
26942677
PMCID:
PMC4781437
DOI:
10.1016/j.molcel.2016.02.008
[Indexed for MEDLINE]
Free PMC Article

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