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

报告人：杨建华中山大学生命科学学院教授

时间：2019年5月20日，10:00-11:30

地点：吕志和楼B106

主持人：伊成器教授

摘要：

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.

个人简介：杨建华，中山大学生命科学学院教授，博士生导师。2008年毕业于中山大学并获得生物化学与分子生物学博士学位。杨建华教授长期致力于开发RNA组学的方法和技术研究RNA的表观遗传调控及功能机制。近5年来，在Nature、Nature Cell Biology、European Urology、Nucleic Acids Res.和Cell Reports等杂志发表20多篇研究论文，9篇研究论文被选为ESI高引用论文，多篇研究论文被Nature Cell Biol.、Nature Reviews Genetics、Nature Chemical Biology和European Urology等杂志亮点评述，1篇论文入选“2014年中国百篇最具影响国际学术论文”。开发的计算机软件和分析平台被引用超过2500次，单篇最高他引超过900次。

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