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 m(6)A RNA modification regulates promoter-proximal RNAP II pausing in Drosophila cells. The m(6)A methyltransferase complex (MTC) and the nuclear reader Ythdc1 are recruited to gene promoters. Depleting the m(6)A 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 m(6)A catalytic domain. Collectively, our data reveal an important link between RNAP II pausing and the m(6)A RNA modification, thus adding another layer to m(6)A-mediated gene regulation.

Automated summary

m(6)A RNA modification regulates RNAP II pausing in Drosophila cells, affecting pause release, Ser2P occupancy, and nascent RNA transcription. The m(6)A-mediated gene regulation adds another layer to the control of gene expression.