M6A RNA methylation regulates promoter proximal pausing of RNA Pol II (DRB-4sU-seq)

ABSTRACT: RNA modification has emerged as an important layer in the control of gene expression. The N6-methyladenosine (m6A) RNA modification is the most prevalent and influences several processes including pre-mRNA splicing, alternative polyadenylation, mRNA decay and translation. Here, we show that m6A regulates transcription by controlling promoter proximal pause release of RNA Pol II. Our results show that the m6A methyltransferase complex together with the nuclear reader Ythdc1 are recruited to gene promoters. Loss of m6A methyltransferase complex leads to increased levels of promoter proximal pausing of RNA Pol II, decrease in Ser2P occupancy on gene body, and affects nascent RNA transcription. Furthermore, we show that the binding of the complex is Spt6-dependent and can be predicted by collective features, with Pol II and pause factors (GAF and M1BP) binding being the most important. We also demonstrate that tethering Mettl3 to a heterologous gene promoter was sufficient to increase the release of RNAP II from the promoter, and this effect was dependent on its m6A catalytic domain. Collectively our data indicate that m6A RNA feeds back to the transcription machinery via its recruitment to the chromatin, and thus uncovering an important link between epigenetic modification of RNA and transcription.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE144245 | GEO | 2021/07/28

REPOSITORIES: GEO