Molecular CellMolecular BiologyPeer-reviewed journal article
METTL3 promotes cell cycle progression via activation of transcriptional elongation.
Azime Akçaöz-AlasariD, Yanhua WangiD, Hang LiiD, Denis Ostapenko, Carlos Andrés Ramírez Parrado, Daniela Villalobos, Hengyi LiiD, Prajwal Chaitanya BodduiD, Alexander NguyeniD, Marcelo Pérez-PepeiD, Pénélope Darnat, Bünyamin AkgüliD, Manoj M. PillaiiD, Yansheng LiuiD, Lilian KabecheiD, Claudio R. AlarcóniD
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.
- organism: human
- assay: metagenomics
- research focus: cell type annotation
- research focus: differential expression
- research focus: gene regulatory network inference
- approach: statistical model
- approach: experimental assay
- Citations
- 0
- FWCI
- 0.00
- Field percentile
- 0th percentile
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