清华大学欧光朔研究组发现RNA编辑可限制过度活跃的纤毛激酶。相关论文发表在2021年8月27日出版的《科学》杂志上。

他们在感觉纤毛损伤的秀丽隐杆线虫中产生了一个组成型活性丝裂原活化蛋白激酶 DYF-5 (DYF-5CA)。遗传抑制筛选确定 ADR-2（一种 RNA 腺苷脱氨酶）的突变挽救了 dyf-5CA 的纤毛表型。他们发现 dyf-5CA 动物异常转录与 dyf-5CA 信使 RNA (mRNA) 配对的反义 RNA，形成双链 RNA，招募 ADR-2 来异位编辑该区域。

RNA 编辑损害了 dyf-5CA mRNA 剪接，由此产生的内含子保留阻止了 DYF-5CA 蛋白翻译并激活了无义介导的 dyf-5CA mRNA 衰减。激酶 RNA 编辑需要激酶过度活跃。类似的依赖于 RNA 编辑的反馈调节限制了其他纤毛激酶 NEKL-4 / NEK10 和 DYF-18 / CCRK，这表明激酶调节的基础是广泛的机制。

据介绍，必须精确调节蛋白激酶活性，但细胞如何控制过度活跃的激酶仍不清楚。

附：英文原文

Title: RNA editing restricts hyperactive ciliary kinases

Author: Dongdong Li, Yufan Liu, Peishan Yi, Zhiwen Zhu, Wei Li, Qiangfeng Cliff Zhang, Jin Billy Li, Guangshuo Ou

Issue&Volume: 2021/08/27

Abstract: Protein kinase activity must be precisely regulated, but how a cell governs hyperactive kinases remains unclear. In this study, we generated a constitutively active mitogen-activated protein kinase DYF-5 (DYF-5CA) in Caenorhabditis elegans that disrupted sensory cilia. Genetic suppressor screens identified that mutations of ADR-2, an RNA adenosine deaminase, rescued ciliary phenotypes of dyf-5CA. We found that dyf-5CA animals abnormally transcribed antisense RNAs that pair with dyf-5CA messenger RNA (mRNA) to form double-stranded RNA, recruiting ADR-2 to edit the region ectopically. RNA editing impaired dyf-5CA mRNA splicing, and the resultant intron retentions blocked DYF-5CA protein translation and activated nonsense-mediated dyf-5CA mRNA decay. The kinase RNA editing requires kinase hyperactivity. The similar RNA editing–dependent feedback regulation restricted the other ciliary kinases NEKL-4/NEK10 and DYF-18/CCRK, which suggests a widespread mechanism that underlies kinase regulation.

DOI: 10.1126/science.abd8971

Source: https://science.sciencemag.org/content/373/6558/984