Decoding the Regulation and Function of RNA modifications from Epitranscriptomic and Epigenomic Data

Speaker：Prof. Jianhua Yang, College of Life Sciences, Zhongshan University.

Time：2019-5-20，10:00-11:30

Place：Lui Che Woo Building B106

Abstract：

N⁶-methyladenosine (m⁶A) is the most prevalent internal post-transcriptional modification in human transcriptome and has been shown to have important roles in various normal and pathological processes. However, the process by which m⁶A is deposited on mRNAs is largely unknown. Here we developed a serial of computational and experimental methods to decode the regulation of m⁶A methylation from epigenomic and epitranscriptomic data and demonstrated that histone H3 trimethylation at Lys36 (H3K36me3), a marker for transcription elongation, guides m6A deposition globally. Comparative analyses of ChIP-seq data for H3K36me3 and m⁶A-seq data revealed that majorities of m⁶A peaks overlapped with H3K36me3 sites and that the overlapping sites were enriched near stop codons. We also found that m⁶A sites identified from miCLIP are enriched in the vicinity of H3K36me3 peaks and are reduced globally when cellular H3K36me3 is depleted.  Furthermore, we show that a significant genome-wide correlation between chromatin binding of METTL14 to H3K36me3. Mechanistically, H3K36me3 is recognized and bound directly by METTL14, a crucial component of the m6A methyltransferase complex (MTC), which in turn facilitates the binding of the m⁶A MTC to adjacent RNA polymerase II, thereby delivering the m⁶A MTC to actively transcribed nascent RNAs to deposit m⁶A co-transcriptionally. The discovery of interplay between modified histones and RNA methylation represents a new regulatory layer, and an additional level of complexity, in the control of gene expression.