美国耶鲁大学Stephanie Halene、Toma Tebaldi、Richard A. Flavell、Yimeng Gao、上海交通大学Hua-Bing Li等研究人员合作发现，m⁶A修饰可防止造血发育过程中内源性双链RNA的形成和有害的先天免疫反应。2020年出版的《免疫学》发表了这项成果。

Title: m6A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development

Author: Yimeng Gao, Radovan Vasic, Yuanbin Song, Rhea Teng, Chengyang Liu, Rana Gbyli, Giulia Biancon, Raman Nelakanti, Kirsten Lobben, Eriko Kudo, Wei Liu, Anastasia Ardasheva, Xiaoying Fu, Xiaman Wang, Poorval Joshi, Veronica Lee, Burak Dura, Gabriella Viero, Akiko Iwasaki, Rong Fan, Andrew Xiao, Richard A. Flavell, Hua-Bing Li, Toma Tebaldi, Stephanie Halene

Issue&Volume: 2020-06-03

Abstract: N6-methyladenosine (m6A) is the most abundant RNA modification, but little is known about its role in mammalianhematopoietic development. Here, we show that conditional deletion of the m6A writer METTL3 in murine fetal liver resulted in hematopoietic failure and perinatallethality. Loss of METTL3 and m6A activated an aberrant innate immune response, mediated by the formation of endogenousdouble-stranded RNAs (dsRNAs). The aberrantly formed dsRNAs were long, highly m6A modified in their native state, characterized by low folding energies, and predominantlyprotein coding. We identified coinciding activation of pattern recognition receptorpathways normally tasked with the detection of foreign dsRNAs. Disruption of the aberrantimmune response via abrogation of downstream Mavs or Rnasel signaling partially rescued the observed hematopoietic defects in METTL3-deficientcells in vitro and in vivo. Our results suggest that m6A modification protects against endogenous dsRNA formation and a deleterious innateimmune response during mammalian hematopoietic development.

DOI: 10.1016/j.immuni.2020.05.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30184-9