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

Michael Aregger, Aneesa Kaskar, Dhaval Varshney, Maria Elena Fernandez-Sanchez, Francisco A. Inesta-Vaquera, Simone Weidlich, Victoria H. Cowling (Lead / Corresponding author)

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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.

Original languageEnglish
Pages (from-to)734-746
Number of pages13
JournalMolecular Cell
Volume61
Issue number5
DOIs
Publication statusPublished - 3 Mar 2016

Fingerprint

Cyclin B1
G1 Phase
Methylation
Messenger RNA
Phosphorylation
Cell Nucleus Active Transport
RNA Polymerase II
Guanosine
G2 Phase
Nuclear Envelope
Methyltransferases
Protein Biosynthesis
Cell Division
mRNA (guanine(N7))-methyltransferase
Cell Cycle
Cell Proliferation
Enzymes
Proteins

Cite this

Aregger, Michael ; Kaskar, Aneesa ; Varshney, Dhaval ; Fernandez-Sanchez, Maria Elena ; Inesta-Vaquera, Francisco A. ; Weidlich, Simone ; Cowling, Victoria H. / CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription. In: Molecular Cell. 2016 ; Vol. 61, No. 5. pp. 734-746.
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CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription. / Aregger, Michael; Kaskar, Aneesa; Varshney, Dhaval; Fernandez-Sanchez, Maria Elena; Inesta-Vaquera, Francisco A.; Weidlich, Simone; Cowling, Victoria H. (Lead / Corresponding author).

In: Molecular Cell, Vol. 61, No. 5, 03.03.2016, p. 734-746.

Research output: Contribution to journalArticle

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