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RESEARCH PRODUCT

m6A RNA methylation regulates promoter proximal pausing of RNA Polymerase II

Junaid AkhtarYad Ghavi-helmSteffen AlbrechtJean-yves RoignantJean-yves RoignantGuillaume JunionYoan RenaudMarion Silies

subject

Regulation of gene expression0303 health sciencesbiologyRNA methylationChemistryMethyltransferase complex[SDV]Life Sciences [q-bio]030302 biochemistry & molecular biologyHeterologousRNA polymerase IIPromoterCell BiologyCell biology[SDV] Life Sciences [q-bio]enzymes and coenzymes (carbohydrates)03 medical and health sciencesGene expressionbiology.proteinbacteriaMolecular BiologyGeneComputingMilieux_MISCELLANEOUS030304 developmental biology

description

AbstractRNA Polymerase II (RNAP II) pausing is essential to precisely control gene expression and is critical for development of metazoans. Here, we show that the m6A RNA modification regulates promoter-proximal RNAP II pausing. The m6A methyltransferase complex (MTC), with the nuclear reader Ythdc1, are recruited to gene promoters. Depleting the m6A MTC leads to a decrease in RNAP II pause release and in Ser2P occupancy on the gene body, and affects nascent RNA transcription. Tethering Mettl3 to a heterologous gene promoter is sufficient to increase RNAP II pause release, an effect that relies on its m6A catalytic domain. Collectively, our data reveal an important link between RNAP II pausing and the m6A RNA modification, thus adding another layer to m6A-mediated gene regulation.

https://doi.org/10.1101/2020.03.05.978163