Epitranscriptomic N6-Methyladenosine Modification Is Required for Direct Lineage Reprogramming into Neurons
Epitranscriptomic N6-Methyladenosine Modification Is Required for Direct Lineage Reprogramming into Neurons
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DOI：
10.1021/acschembio.0c00265
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发表时间：
2020-08-21
影响因子：
4
通讯作者：
Kim, Jongpil
中科院分区：
文献类型：
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作者：
Choi, Hwan;Baek, Soonbong;Kim, Jongpil
N-6-甲基腺苷（N-6-methyladenosine，m（6）A）是真核生物mRNA的一种保守的表位转录修饰，在多种生物学过程中起着重要作用。在这里，我们报道了m（6）A修饰在控制直接谱系重编程为诱导的神经元细胞（iN）中起关键作用。我们发现m（6）A修饰是神经元直接转换所需的特定mRNA重塑所必需的。通过Mettl 3敲低抑制m（6）A甲基化降低了直接谱系重编程的效率，而通过Mettl 3过表达增加m（6）A甲基化增加了iN产生的效率。此外，我们发现转录因子Btg 2是m（6）A修饰的有效iN产生的功能靶标。综上所述，我们的结果表明，建立epitranscriptomic重塑的细胞命运转化为iNs的重要性。
N-6-methyladenosine (m(6)A), a conserved epitranscriptomic modification of eukaryotic mRNA (mRNA), plays a critical role in a variety of biological processes. Here, we report that m(6)A modification plays a key role in governing direct lineage reprogramming into induced neuronal cells (iNs). We found that m(6)A modification is required for the remodeling of specific mRNAs required for the neuronal direct conversion. Inhibition of m(6)A methylation by Mettl3 knockdown decreased the efficiency of direct lineage reprogramming, whereas increased m(6)A methylation by Mettl3 overexpression increased the efficiency of iN generation. Moreover, we found that transcription factor Btg2 is a functional target of m(6)A modification for efficient iN generation. Taken together, our results suggest the importance of establishing epitranscriptomic remodeling for the cell fate conversion into iNs.