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bioRxiv · 10.1101/2025.07.12.664541

METTL3 promotes cell cycle progression via activation of transcriptional elongation.

Alarcon, C.
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Abstract

Transcription elongation through the phosphorylation of RNA Pol II by CDK9 (P-TEFb) is not only required for mRNA transcription to produce proteins, but is a fundamental mechanism required for proper cell cycle progression. N6-methyladenosine (m6A) methyltransferase METTL3 methylates mRNAs co-transcriptionally, modulating their downstream processing as well as the non-coding RNA 7SK post-transcriptionally. We found that CDK1 phosphorylates METTL3 at Ser43 at the onset of mitosis. This METTL3 phosphorylation promotes transcriptional elongation via the m6A/7SK/P-TEFb axis, allowing RNA Pol II clearance and proper cell cycle progression. Disruption of this pathway results in defects in chromosome segregation. Our findings establish a novel mechanistic link between CDK1 regulation of transcriptional elongation through activation of METTL3 and RNA methylation.

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Alarcon, C.. 2025-07-17. METTL3 promotes cell cycle progression via activation of transcriptional elongation.. https://doi.org/10.1101/2025.07.12.664541

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