m[superscript 6]A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells
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Dedon_m6a RNA.pdf
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Author(s)
Batista, Pedro J.
Molinie, Benoit
Wang, Jinkai
Qu, Kun
Zhang, Jiajing
Li, Lingjie
Bouley, Donna M.
Lujan, Ernesto
Haddad, Bahareh
Daneshvar, Kaveh
Alternative Title
m6A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells
Date Issued
October 2014
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Batista, Pedro J. et al. “m6A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells.” Cell Stem Cell 15.6 (2014): 707–719.
Version
Author's final manuscript
Abstract
N6-methyl-adenosine (m[superscript 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[superscript 6]A by mapping the m[superscript 6]A methylome in mouse and human embryonic stem cells. Thousands of messenger and long noncoding RNAs show conserved m[superscript 6]A modification, including transcripts encoding core pluripotency transcription factors. m[superscript 6]A is enriched over 3′ 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[superscript 6]A methylases, led to m[superscript 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[superscript 6]A is a mark of transcriptome flexibility required for stem cells to differentiate to specific lineages.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.stem.2014.09.019
