【beat365·大學堂】Gene expression regulation by RNA methylation

　　　　報告人簡介

何川教授　　

　　美國藝術與科學院院士，芝加哥大學John T. Wilson講席教授，霍華德休斯醫學研究所研究員，2023年沃爾夫化學獎得主。何川于1994年獲得中國科學技術大學學士學位，2000年獲得麻省理工學院博士學位，2000-2002年在哈佛大學進行博士後研究，于2002年加入芝加哥大學化學系任教至今，2013年入選霍華德休斯醫學研究所研究員。何川教授是研究RNA轉錄後修飾的國際頂尖學者，他的實驗室在2011年發現了可逆RNA甲基化修飾及其在基因表達調控中的作用，開創了一個全新的研究領域；2020年又發現了RNA甲基化修飾調控染色質狀态和轉錄的生物學功能。此外他的實驗室也開發了多項用于研究RNA、DNA修飾和基因調控方面的檢測技術。

Dr. He is the John T. Wilson Distinguished Service Professor in the Department of Chemistry and Department of Biochemistry and Molecular Biology at the University of Chicago. He received his bachelor of science degree in 1994 from the University of Science and Technology of China and his Ph.D. in chemistry from the Massachusetts Institute of Technology in 2000, studying under professor Stephen J. Lippard. After training as a Damon-Runyon postdoctoral fellow with professor Gregory L. Verdine at Harvard University, he joined the University of Chicago as an assistant professor, rising to associate professor in 2008 and full professor in 2010. He was selected as an investigator of the Howard Hughes Medical Institute in 2013. Dr. He’s research spans a broad range of fields including chemical biology, RNA biology, epigenetics, biochemistry, and genomics. His recent research concerns reversible RNA and DNA methylation in biological regulation. In 2011, his group discovered reversible RNA methylation as a new mechanism of gene expression regulation. His laboratory characterized the RNA m⁶A methyltransferase complex and several key reader proteins that bind preferentially to m⁶A-modified RNA and regulate their stability and translation. In 2020, Dr. He’s laboratory reported prevalent m⁶A methylation on chromatin-associated regulatory RNAs (carRNAs), which regulates chromatin state and global transcription. The reversible methylation of carRNA controls mammalian and plant development. His laboratory also spearheaded the development of enabling technologies to study RNA and DNA modifications as well as gene expression regulation.

　　報告摘要

Over 150 types of post-transcriptional RNA modifications have been identified in all kingdoms of life. We have discovered RNA demethylation and shown that reversible RNA modification could impact a wide range of biological processes. We have also characterized proteins that selectively recognize m⁶A-modified mRNA and affect the translation status and lifetime of the target RNA. I will present our recent discoveries on chromatin state regulation by chromatin-associated regulatory RNA (carRNA) methylation. We found that carRNAs contain different chemical marks which facilitate recruitment of chromatin factors to shape local and global chromatin state. Some of these carRNA methylation-dependent pathways explain oncogenic roles of well-known oncogenes, which provides potential new targets for future anti-cancer therapies.