Epitranscriptomic N6-Methyladenosine Modification Is Required for Direct Lineage Reprogramming into Neurons.,ACS Chemical Biology

当前位置： X-MOL 学术 › ACS Chem. Biol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Epitranscriptomic N6-Methyladenosine Modification Is Required for Direct Lineage Reprogramming into Neurons.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-07-07 , DOI: 10.1021/acschembio.0c00265
Hwan Choi ₁ , Soonbong Baek ₂ , Byounggook Cho ₁ , Siyoung Kim ₁ , Junyeop Kim ₁ , Yujung Chang ₁ , Jaein Shin ₁ , Jongpil Kim _{1,

3}

Affiliation

N⁶-methyladenosine (m⁶A), a conserved epitranscriptomic modification of eukaryotic mRNA (mRNA), plays a critical role in a variety of biological processes. Here, we report that m⁶A modification plays a key role in governing direct lineage reprogramming into induced neuronal cells (iNs). We found that m⁶A modification is required for the remodeling of specific mRNAs required for the neuronal direct conversion. Inhibition of m⁶A methylation by Mettl3 knockdown decreased the efficiency of direct lineage reprogramming, whereas increased m⁶A methylation by Mettl3 overexpression increased the efficiency of iN generation. Moreover, we found that transcription factor Btg2 is a functional target of m⁶A modification for efficient iN generation. Taken together, our results suggest the importance of establishing epitranscriptomic remodeling for the cell fate conversion into iNs.

中文翻译：

直接谱系重编程为神经元需要表观转录组学 N6-甲基腺苷修饰。

N ⁶ -甲基腺苷(m ⁶ A) 是真核 mRNA (mRNA) 的一种保守的表观转录组修饰，在多种生物过程中发挥着关键作用。在这里，我们报告 m ⁶ A 修饰在控制直接谱系重编程为诱导神经元细胞 (iNs) 中起着关键作用。我们发现，神经元直接转换所需的特定 mRNA 的重塑需要m ⁶ A 修饰。Mettl3 敲低对 m ⁶ A 甲基化的抑制降低了直接谱系重编程的效率，而增加了 m ⁶Mettl3 过表达的甲基化提高了 iN 生成的效率。此外，我们发现转录因子 Btg2 是有效 iN 生成的 m ⁶ A 修饰的功能目标。总之，我们的结果表明建立表观转录组重构对细胞命运转化为 iN 的重要性。

更新日期：2020-08-21

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11