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RNA fate determination through co-transcriptional methylation of newely synthesized transcripts

ABSTRACT: Using murine embryonic stem (mES) cells, here we show that two RNAi factors, Dgcr8 and the RNAseIII Drosha, physically associate with chromatin. We found that these known microRNA-processing factors associate with a subset of actively transcribed genes, as well as non-coding genes, including snoRNA, and lncRNA genes. Dgcr8 recruitment to chromatin was dependent on Methyltransferase-like 3 (Mettl3), which catalyzes N6-methyladenosine (m6A) of RNAs. Chemical inhibition of RNA polymerase II (RNAPII) disrupted the association of Dgcr8 and Mettl3 with chromatin, strongly suggesting RNA methylation and processing events occur co-transcriptionally. We also found that temperature stress causes a radical relocalization of Dgcr8 and Mettl3 to stress-induced genes including Hsp70. Genetic ablation of Dgcr8 or Mettl3 led to the accumulation of Hsp70 mRNA, elongation of its half-life, and increased protein levels only in cells subjected to acute heat stress. This indicates that acute heat-stress co-transcriptionally marks Hsp70 mRNAs by Mettl3 and Dgcr8 for subsequent RNA degradation to control the timing and magnitude of the heat shock response.

ORGANISM(S): Mus musculus

PROVIDER: GSE92257 | GEO | 2017/05/18

SECONDARY ACCESSION(S): PRJNA357047

REPOSITORIES: GEO

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