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

      日期: 2019-05-14
      題目:Decoding the Regulation and Function of RNA modifications from Epitranscriptomic and Epigenomic Data
      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.
      楊建華,中山大學生命科學學院教授,博士生導師。2008年畢業于中山大學并獲得生物化學與分子生物學博士學位。楊建華教授長期致力于開發RNA組學的方法和技術研究RNA的表觀遺傳調控及功能機制。近5年來,在Nature、Nature Cell Biology、European Urology、Nucleic Acids Res.和Cell Reports等雜志發表20多篇研究論文,9篇研究論文被選為ESI高引用論文,多篇研究論文被Nature Cell Biol.、Nature Reviews Genetics、Nature Chemical Biology和European Urology等雜志亮點評述,1篇論文入選“2014年中國百篇最具影響國際學術論文”。開發的計算機軟件和分析平臺被引用超過2500次,單篇最高他引超過900次。