m6A RNA methylation regulates promoter proximal pausing of RNA Polymerase II

RNA 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 re...

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Published inbioRxiv
Main Authors Akhtar, Junaid, Renaud, Yoan, Albrecht, Steffen, Ghavi-Helm, Yad, Jean-Yves Roignant, Silies, Marion, Junion, Guillaume
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 07.03.2020
Subjects
DNA methylation
DNA-directed RNA polymerase
Gene expression
Gene regulation
Methyltransferase
N6-methyladenosine
RNA modification
RNA polymerase
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Summary:RNA 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. Footnotes * The resolution of the figures is corrected, which was suboptimal in earlier conversion
DOI:10.1101/2020.03.05.978163