重编程
生物
小RNA
诱导多能干细胞
胚胎干细胞
转录组
细胞生物学
N6-甲基腺苷
核糖核酸
甲基化
基因表达
遗传学
细胞
基因表达调控
基因
甲基转移酶
作者
Tong Chen,Yajuan Hao,Ying Zhang,Miaomiao Li,Meng Wang,Weifang Han,WU Yong-sheng,Ying Lv,Jie Hao,Yunlong Wang,Ang Li,Ying Yang,Kang-Xuan Jin,Zhi-Hong Xu,Yuhuan Li,Xiao-Li Ping,Weiyi Lai,Ligang Wu,Guibin Jiang,Hailin Wang,Lisi Sang,Xiujie Wang,Qi Zhou
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2015-03-01
卷期号:16 (3): 289-301
被引量:458
标识
DOI:10.1016/j.stem.2015.01.016
摘要
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.
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