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Home > Active Motif's Podcast > Influence of Dynamic RNA Methylation on Gene Expression (Chuan He)


	Podcast:		Active Motif's Podcast
	Episode:		Influence of Dynamic RNA Methylation on Gene Expression (Chuan He)
	Category:		Science & Medicine
	Duration:		00:41:22
	Publish Date:		2020-08-20 02:59:11
	Description:		In this episode of the Epigenetics Podcast, we caught up with Dr. Chuan He, John T. Wilson Distinguished Service Professor at the University of Chicago, to talk about his work on the influence of dynamic RNA methylation on gene expression. More than 150 structurally distinct post-transcriptional modifications of RNA have been identified at thousands of sites in cellular RNA molecules. Some RNA modifications are dynamic and may have critical regulatory roles analogous to modifications of protein and DNA. Understanding the scope and mechanisms of dynamic RNA modifications thus represents an emerging research frontier in biology and medicine. The internal N6-methyladenosine (m6A) modification in messenger RNA (mRNA) is one of the most abundant RNA modifications in eukaryotes. On average, this RNA base modification is present in approximately 3 sites in every mammalian mRNA molecule. The m6A modification has been shown to be critically important for cellular differentiation, animal development, and a range of biological signaling and stress responses. In 2011, Chuan He's lab reported that m6A in mammalian mRNA can be oxidatively demethylated in vitro and inside cells by the enzyme FTO (a fat mass and obesity-associated protein), a major obesity factor This discovery identified FTO as the first known RNA demethylase. Chuan He’s lab also subsequently identified ALKBH5 as the second RNA demethylase that controls mammalian spermatogenesis. More recent work in the He lab has focused on characterization of the YTH family proteins as the “reader” proteins that detect and bind methylated RNAs in mammalian cells to regulate their stability and translation. Functional characterizations revealed that YTHDF2 regulates cytoplasmic localization and mediates the decay of methylated mRNA, YTHDF1 promotes translation of methylated mRNA by facilitating translation initiation, and other methylated RNA readers also contribute to the regulation of mRNA storage, transport, and cellular localization. Research in the He lab also identified a core protein complex comprised of two subunits: METTL3 and METTL14, and an accessory factor WTAP, which mediates cellular m6A RNA methylation. Cellular RNA methylation levels can have profound impacts on normal cellular differentiation and cancer cell proliferation. Their current work focuses on how the methylation selectivity is achieved. In this interview, we discuss the story on how the He lab discovered the members of the family of proteins that read, write, and erase RNA modifications and the mechanisms of how those RNA modifications act in the field of epigenetics. References Guifang Jia, Cai-Guang Yang, … Chuan He (2008) Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO (FEBS letters) DOI: 10.1016/j.febslet.2008.08.019 Guifang Jia, Ye Fu, … Chuan He (2011) N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO (Nature Chemical Biology) DOI: 10.1038/nchembio.687 Guanqun Zheng, John Arne Dahl, … Chuan He (2013) ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility (Molecular Cell) DOI: 10.1016/j.molcel.2012.10.015 Jianzhao Liu, Yanan Yue, … Chuan He (2014) A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation (Nature Chemical Biology) DOI: 10.1038/nchembio.1432 Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on Linked-In Active Motif on Facebook eMail: podcast@activemotif.com
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