title: CDK1-Cyclin B1 Activates RNMT, Coordinating mRNA Cap Methylation with G1 Phase Transcription.
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.
authors.affiliation: Centre for Gene Regulation and Expression/MRC Phosphorylation and Ubiquitylation, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Aregger
authors.affiliation: Centre for Gene Regulation and Expression/MRC Phosphorylation and Ubiquitylation, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Aneesa
authors.initials: A
authors.lastname: Kaskar
authors.affiliation: Centre for Gene Regulation and Expression/MRC Phosphorylation and Ubiquitylation, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Dhaval
authors.initials: D
authors.lastname: Varshney
authors.affiliation: Centre for Gene Regulation and Expression/MRC Phosphorylation and Ubiquitylation, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Fernandez-Sanchez
authors.affiliation: Centre for Gene Regulation and Expression/MRC Phosphorylation and Ubiquitylation, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Inesta-Vaquera
authors.affiliation: Division of Signal Transduction Therapy, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: Weidlich
authors.affiliation: 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.
authors.forename: Victoria H
authors.initials: VH
authors.lastname: Cowling
mesh_terms: D016203:CDC2 Protein Kinase; D049109:Cell Proliferation; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D016193:G1 Phase; D016195:G2 Phase; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016196:S Phase; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; C490630:KPNA2 protein, human; D012315:RNA Caps; D012333:RNA, Messenger; D028901:alpha Karyopherins; D008780:Methyltransferases; C055097:mRNA (guanine(N7))-methyltransferase; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases