m6A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells

被引：1013

作者：

Batista, Pedro J. ^{[1
,2
]}

Molinie, Benoit ^{[3
]}

Wang, Jinkai

Qu, Kun ^{[1
,2
]}

Zhang, Jiajing ^{[1
,2
,4
]}

Li, Lingjie ^{[1
,2
]}

Bouley, Donna M. ^{[5
]}

Lujan, Ernesto ^{[6
,7
,8
]}

Haddad, Bahareh ^{[6
,7
]}

Daneshvar, Kaveh ^{[3
]}

Carter, Ava C. ^{[1
,2
]}

Flynn, Ryan A. ^{[1
,2
]}

Zhou, Chan ^{[3
]}

Lim, Kok-Seong ^{[9
]}

Dedon, Peter ^{[9
]}

Wernig, Marius ^{[6
,7
]}

Mullen, Alan C. ^{[3
,10
]}

Xing, Yi ^{[4
]}

Giallourakis, Cosmas C. ^{[3
,10
]}

Chang, Howard Y. ^{[1
,2
]}

机构：

[1] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA

[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA

[4] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[5] Stanford Univ, Sch Med, Dept Comparat Med, Stanford, CA 94305 USA

[6] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[7] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

[8] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA

[9] MIT, Dept Biol Engn, Cambridge, MA 02139 USA

[10] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

来源：

CELL STEM CELL | 2014年 / 15卷 / 06期

关键词：

LONG NONCODING RNA; MESSENGER-RNA; LINEAGE SPECIFIERS; SACCHAROMYCES-CEREVISIAE; POSTNATAL-DEVELOPMENT; NUCLEAR-RNA; PLURIPOTENCY; MOUSE; METHYLATION; REVEALS;

D O I：

10.1016/j.stem.2014.09.019

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

N6-methyl-adenosine (m(6)A) is the most abundant modification on messenger RNAs and is linked to human diseases, but its functions in mammalian development are poorly understood. Here we reveal the evolutionary conservation and function of m(6)A by mapping the m(6)A methylome in mouse and human embryonic stem cells. Thousands of messenger and long noncoding RNAs show conserved m(6)A modification, including transcripts encoding core pluripotency transcription factors. m(6)A is enriched over 30 untranslated regions at defined sequence motifs and marks unstable transcripts, including transcripts turned over upon differentiation. Genetic inactivation or depletion of mouse and human Mettl3, one of the m(6)A methylases, led to m(6)A erasure on select target genes, prolonged Nanog expression upon differentiation, and impaired ESC exit from self-renewal toward differentiation into several lineages in vitro and in vivo. Thus, m(6)A is a mark of transcriptome flexibility required for stem cells to differentiate to specific lineages.

引用

页码：707 / 719

页数：13

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