N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-02

AUTHORS

Yang Wang, Yue Li, Julia I. Toth, Matthew D. Petroski, Zhaolei Zhang, Jing Crystal Zhao

ABSTRACT

N(6)-methyladenosine (m(6)A) has been identified as the most abundant internal modification of messenger RNA in eukaryotes. m(6)A modification is involved in cell fate determination in yeast and embryo development in plants. Its mammalian function remains unknown but thousands of mammalian mRNAs and long non-coding RNAs (lncRNAs) show m(6)A modification and m(6)A demethylases are required for mammalian energy homeostasis and fertility. We identify two proteins, the putative m(6)A MTase, methyltransferase-like 3 (Mettl3; ref. ), and a related but uncharacterized protein Mettl14, that function synergistically to control m(6)A formation in mammalian cells. Knockdown of Mettl3 and Mettl14 in mouse embryonic stem cells (mESCs) led to similar phenotypes, characterized by lack of m(6)A RNA methylation and lost self-renewal capability. A large number of transcripts, including many encoding developmental regulators, exhibit m(6)A methylation inversely correlated with mRNA stability and gene expression. The human antigen R (HuR) and microRNA pathways were linked to these effects. This gene regulatory mechanism operating in mESCs through m(6)A methylation is required to keep mESCs at their ground state and may be relevant to thousands of mRNAs and lncRNAs in various cell types. More... »

PAGES

191-198

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb2902

DOI

http://dx.doi.org/10.1038/ncb2902

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049362451

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24394384


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