CDK1 links RNA methylation to mitosis progression

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Research HighlightPublished: 03 September 2026Cell cycleLisa Heinke1 Nature Reviews Molecular Cell Biology (2026) Cite this articleSave articleView saved researchTranscription is tightly regulated throughout the cell cycle, particularly through the control of transcription elongation. A key regulator of this process is positive transcription elongation factor b (P-TEFb), which phosphorylates RNA polymerase II (Pol II) and releases it from promoter-proximal pausing into productive elongation. During early mitosis, this activity promotes the clearance of Pol II complexes from chromatin, facilitating the global transcription shutdown required for chromosome condensation and accurate mitosis progression. Akçaöz-Alasar, Wang et al. now show how P-TEFb is activated during mitosis.A previous study had found that growth factor signalling induces phosphorylation of METTL3 at Ser43, enabling methylation of the non-coding RNA 7SK. This modification promotes release of P-TEFb from an inhibitory complex composed of 7SK and HEXIM1, thereby activating transcription elongation. This finding prompted the authors to assess phosphorylation of METTL3 at Ser43 during mitosis. Ser43 phosphorylation increased strongly following mitosis entry, suggesting direct regulation by cell-cycle-dependent signalling. Indeed, a cyclin-dependent kinase 1 (CDK1) inhibitor abolished METTL3 phosphorylation. Furthermore, depletion of CDK1 reduced Ser43 phosphorylation and purified CDK1–cyclin B complexes directly phosphorylated METTL3 in vitro, identifying CDK1 as the primary kinase responsible for METTL3 phosphorylation during mitosis.This is a preview of subscription content, access via your institutionAccess options Access through your institutionAccess Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription27,99 € / 30 dayscancel any timeLearn moreSubscribe to this journalReceive 12 print issues and online access269,00 € per yearonly 22,42 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to the full article PDF.39,95 €Prices may be subject to local taxes which are calculated during checkoutSubjectsMitosisTranscriptionReferencesOriginal articleAkçaöz-Alasar, A. et al. METTL3 promotes cell-cycle progression via activation of transcriptional elongation. Mol. Cell 86, 3213–3222.e5 (2026)Article  PubMed  Google Scholar Related articleMimoso, C. A. et al. Regulation of RNA transcript elongation in metazoans and its relevance to disease. Nat. Rev. Mol. Cell Biol. https://doi.org/10.1038/s41580-026-01003-w (2026)Article  PubMed  Google Scholar Download referencesAuthor informationAuthors and AffiliationsNature Reviews Molecular Cell Biology http://www.nature.com/nrm/Lisa HeinkeAuthorsLisa HeinkeView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to Lisa Heinke.Rights and permissionsReprints and permissionsAbout this article