m 6 A Modification Prevents Formation of Endogenous Double-Stranded RNAs and Deleterious Innate Immune Responses during Hematopoietic Development

• Published in: Immunity (Cambridge, Mass.) Vol. 52; no. 6; p. 1007
• Main Authors: Gao, Yimeng, Vasic, Radovan, Song, Yuanbin, Teng, Rhea, Liu, Chengyang, Gbyli, Rana, Biancon, Giulia, Nelakanti, Raman, Lobben, Kirsten, Kudo, Eriko, Liu, Wei, Ardasheva, Anastasia, Fu, Xiaoying, Wang, Xiaman, Joshi, Poorval, Lee, Veronica, Dura, Burak, Viero, Gabriella, Iwasaki, Akiko, Fan, Rong, Xiao, Andrew, Flavell, Richard A, Li, Hua-Bing, Tebaldi, Toma, Halene, Stephanie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 16.06.2020
• Subjects: Adenosine - chemistry; Animals; Biomarkers; Bone marrow; Bone Marrow Failure Disorders - etiology; Bone Marrow Failure Disorders - metabolism; Bone Marrow Failure Disorders - pathology; Cell Differentiation - genetics; Defects; Disease Models, Animal; Double-stranded RNA; Epigenesis, Genetic; Fetuses; Gene Expression; Genes; Hematopoiesis - genetics; Hematopoiesis - immunology; Hematopoietic Stem Cells; Immune response; Immune system; Immunity, Innate - genetics; Immunophenotyping; Innate immunity; Lethality; Leukemia; Liver; Liver diseases; Mammals; Methylation; Methyltransferases - genetics; Methyltransferases - metabolism; Mice; Mice, Knockout; N6-methyladenosine; Pattern recognition; Pattern recognition receptors; Protein folding; RNA modification; RNA, Double-Stranded - chemistry; RNA, Double-Stranded - metabolism; Stem cells; dsRNA; RNA modification; hematopoietic development; N-methyladenosine; hematopoiesis; innate immune response; METTL3; m6A; epitranscriptome; double-stranded RNA

N -methyladenosine (m A) is the most abundant RNA modification, but little is known about its role in mammalian hematopoietic development. Here, we show that conditional deletion of the m A writer METTL3 in murine fetal liver resulted in hematopoietic failure and perinatal lethality. Loss of METTL3...