Comparative Functional RNA Editomes of Neural Differentiation from Human PSCs
Comparative Functional RNA Editomes of Neural Differentiation from Human PSCs
复制标题
人类 PSC 神经分化的比较功能性 RNA 编辑组
DOI：
10.1093/lifemedi/lnac027
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发表时间：
2022-08
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
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作者：
Zhang Y;Zhang Q;Hou YH;Wang R;Wang Y
摘要RNA编辑是构成表转录组复杂性的基本机制。A-to-G编辑是ADAR 1和ADAR 2在人体中催化的主要类型。使用CRISPR/Cas9方法敲除ADAR 1/2，我们确定了RNA编辑在人胚胎干细胞（hESC）向神经祖细胞（NPC）定向分化中的调节作用。分析了hESC中A-to-G编辑的全基因组景观和代表所有三个胚层和胚外细胞命运的四种衍生细胞谱系，特别关注神经分化。此外，生物信息学指导的案例研究确定了ZYG 11B 3 'UTR中的潜在功能编辑事件，该事件可能通过获得miR 6089靶向在NPC分化的调节中发挥作用。总的来说，我们的研究确立了A-to-G RNA编辑在神经谱系分化中的功能作用;说明了hESC和NPC分化的RNA编辑景观;并为其分子见解提供了新的见解。
Abstract RNA editing is a fundamental mechanism that constitutes the epitranscriptomic complexity. A-to-G editing is the predominant type catalyzed by ADAR1 and ADAR2 in human. Using a CRISPR/Cas9 approach to knockout ADAR1/2, we identified a regulatory role of RNA editing in directed differentiation of human embryonic stem cells (hESCs) towards neural progenitor cells (NPCs). Genome-wide landscapes of A-to-G editing in hESCs and four derivative cell lineages representing all three germ layers and the extraembryonic cell fate were profiled, with a particular focus on neural differentiation. Further, a bioinformatics-guided case study identified a potential functional editing event in ZYG11B 3'UTR that might play a role in regulation of NPC differentiation through gain of miR6089 targeting. Collectively, our study established the functional role of A-to-G RNA editing in neural lineage differentiation; illustrated the RNA editing landscapes of hESCs and NPC differentiation; and shed new light on molecular insights thereof.