RNA-seq and small RNA-seq from WT and ADAR1 knockdown H9 lines and their differentiation to specific types of neurons

Adenosine deaminases acting on RNA (ADARs) are involved in adenosine (A) to inosine (I) RNA editing and human ADARs are implicated in neurological diseases. Here we generated human embryonic stem cells (hESCs) lacking ADAR1 to investigate its role in neural development in a human context. We found that ADAR1 deficiency significantly retarded neural induction with widespread mRNA and miRNA expression changes. We have genome widely examined the changes of A-to-I editing and miRNA expression after ADAR1 knockdown. Such aberrant mRNA and miRNA expression was not due to reduced A-to-I editing after ADAR1 knockdown. We further revealed that ADAR1 regulates miRNA biogenesis independent of its editing activity.

作用于RNA的腺苷脱氨酶（Adenosine deaminases acting on RNA, ADARs）可介导腺苷（A）向肌苷（I）的RNA编辑过程，人类ADARs与神经系统疾病密切相关。本研究构建了缺失ADAR1的人类胚胎干细胞（human embryonic stem cells, hESCs），以在人类生理背景下探究其在神经发育中的调控功能。研究发现，ADAR1缺陷会显著延缓神经诱导进程，并伴随广泛的信使RNA（messenger RNA, mRNA）和微小RNA（microRNA, miRNA）表达谱改变。我们对ADAR1敲低后全基因组范围内的A-to-I编辑及miRNA表达变化进行了系统检测。结果表明，此类异常的mRNA与miRNA表达并非由ADAR1敲低后A-to-I编辑水平降低所导致；进一步研究证实，ADAR1能够独立于其编辑活性调控miRNA的生物发生。