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m6A RNA Methylation Is Regulated by MicroRNAs and Promotes Reprogramming to Pluripotency
Tong Chen,Ya-Juan Hao,Ying Zhang, Miao-Miao Li,Meng Wang,Weifang Han,Yongsheng Wu,Ying Lv,Jie Hao,Libin Wang,Ang Li,Ying Yang,Kang-Xuan Jin,Xu Zhao,Yuhuan Li,Xiao-Li Ping,Wei-Yi Lai,Li-Gang Wu,Guibin Jiang,Hai-Lin Wang,Lisi Sang,Xiu-Jie Wang,Yun-Gui Yang and Qi Zhou
Cell Stem Cell
Abstract
N6-methyladenosine (m6A) 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 m6A modification profiles in the mRNA transcriptomes of four cell types with different degrees of pluripotency. Comparative analysis reveals several features of m6A, especially gene- and cell-type-specific m6A mRNA modifications. We also show that microRNAs (miRNAs) regulate m6A modification via a sequence pairing mechanism. Manipulation of miRNA expression or sequences alters m6A modification levels through modulating the binding of METTL3 methyltransferase to mRNAs containing miRNA targeting sites. Increased m6A abundance promotes the reprogramming of mouse embryonic fibroblasts (MEFs) to pluripotent stem cells; conversely, reduced m6A levels impede reprogramming. Our results therefore uncover a role for miRNAs in regulating m6A formation of mRNAs and provide a foundation for future functional studies of m6A modification in cell reprogramming.
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DOI:10.1016/j.stem.2015.01.016 |
论文题目: |
m6A RNA Methylation Is Regulated by MicroRNAs and Promotes Reprogramming to Pluripotency |
英文论文题目: |
m6A RNA Methylation Is Regulated by MicroRNAs and Promotes Reprogramming to Pluripotency |
第一作者: |
Tong Chen,Ya-Juan Hao,Ying Zhang, Miao-Miao Li,Meng Wang,Weifang Han,Yongsheng Wu,Ying Lv,Jie Hao,Libin Wang,Ang Li,Ying Yang,Kang-Xuan Jin,Xu Zhao,Yuhuan Li,Xiao-Li Ping,Wei-Yi Lai,Li-Gang Wu,Guibin Jiang,Hai-Lin Wang,Lisi Sang,Xiu-Jie Wang,Yun-Gui Yang and Qi Zhou |
英文第一作者: |
Tong Chen,Ya-Juan Hao,Ying Zhang, Miao-Miao Li,Meng Wang,Weifang Han,Yongsheng Wu,Ying Lv,Jie Hao,Libin Wang,Ang Li,Ying Yang,Kang-Xuan Jin,Xu Zhao,Yuhuan Li,Xiao-Li Ping,Wei-Yi Lai,Li-Gang Wu,Guibin Jiang,Hai-Lin Wang,Lisi Sang,Xiu-Jie Wang,Yun-Gui Yang and Qi Zhou |
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2015-02-13 |
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摘要: |
N6-methyladenosine (m6A) 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 m6A modification profiles in the mRNA transcriptomes of four cell types with different degrees of pluripotency. Comparative analysis reveals several features of m6A, especially gene- and cell-type-specific m6A mRNA modifications. We also show that microRNAs (miRNAs) regulate m6A modification via a sequence pairing mechanism. Manipulation of miRNA expression or sequences alters m6A modification levels through modulating the binding of METTL3 methyltransferase to mRNAs containing miRNA targeting sites. Increased m6A abundance promotes the reprogramming of mouse embryonic fibroblasts (MEFs) to pluripotent stem cells; conversely, reduced m6A levels impede reprogramming. Our results therefore uncover a role for miRNAs in regulating m6A formation of mRNAs and provide a foundation for future functional studies of m6A modification in cell reprogramming. |
英文摘要: |
N6-methyladenosine (m6A) 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 m6A modification profiles in the mRNA transcriptomes of four cell types with different degrees of pluripotency. Comparative analysis reveals several features of m6A, especially gene- and cell-type-specific m6A mRNA modifications. We also show that microRNAs (miRNAs) regulate m6A modification via a sequence pairing mechanism. Manipulation of miRNA expression or sequences alters m6A modification levels through modulating the binding of METTL3 methyltransferase to mRNAs containing miRNA targeting sites. Increased m6A abundance promotes the reprogramming of mouse embryonic fibroblasts (MEFs) to pluripotent stem cells; conversely, reduced m6A levels impede reprogramming. Our results therefore uncover a role for miRNAs in regulating m6A formation of mRNAs and provide a foundation for future functional studies of m6A modification in cell reprogramming. |
刊物名称: |
Cell Stem Cell |
英文刊物名称: |
Cell Stem Cell |
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其它备注: |
Tong Chen,Ya-Juan Hao,Ying Zhang, Miao-Miao Li,Meng Wang,Weifang Han,Yongsheng Wu,Ying Lv,Jie Hao,Libin Wang,Ang Li,Ying Yang,Kang-Xuan Jin,Xu Zhao,Yuhuan Li,Xiao-Li Ping,Wei-Yi Lai,Li-Gang Wu,Guibin Jiang,Hai-Lin Wang,Lisi Sang,Xiu-Jie Wang,Yun-Gui Yang and Qi Zhou. m6A RNA Methylation Is Regulated by MicroRNAs and Promotes Reprogramming to Pluripotency. Cell Stem Cell. DOI:10.1016/j.stem.2015.01.016 |
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