| Literature DB >> 25683224 |
Tong Chen1, Ya-Juan Hao2, Ying Zhang3, Miao-Miao Li2, Meng Wang4, Weifang Han5, Yongsheng Wu6, Ying Lv2, Jie Hao3, Libin Wang5, Ang Li2, Ying Yang2, Kang-Xuan Jin2, Xu Zhao2, Yuhuan Li3, Xiao-Li Ping2, Wei-Yi Lai7, Li-Gang Wu8, Guibin Jiang7, Hai-Lin Wang7, Lisi Sang5, Xiu-Jie Wang9, Yun-Gui Yang10, Qi Zhou11.
Abstract
N(6)-methyladenosine (m(6)A) has been recently identified as a conserved epitranscriptomic modification of eukaryotic mRNAs, but its features, regulatory mechanisms, and functions in cell reprogramming are largely unknown. Here, we report m(6)A modification profiles in the mRNA transcriptomes of four cell types with different degrees of pluripotency. Comparative analysis reveals several features of m(6)A, especially gene- and cell-type-specific m(6)A mRNA modifications. We also show that microRNAs (miRNAs) regulate m(6)A modification via a sequence pairing mechanism. Manipulation of miRNA expression or sequences alters m(6)A modification levels through modulating the binding of METTL3 methyltransferase to mRNAs containing miRNA targeting sites. Increased m(6)A abundance promotes the reprogramming of mouse embryonic fibroblasts (MEFs) to pluripotent stem cells; conversely, reduced m(6)A levels impede reprogramming. Our results therefore uncover a role for miRNAs in regulating m(6)A formation of mRNAs and provide a foundation for future functional studies of m(6)A modification in cell reprogramming.Entities:
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Year: 2015 PMID： 25683224 DOI： 10.1016/j.stem.2015.01.016
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633