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.

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。在这项研究中，我们在破坏感觉纤毛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。我们发现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 以异位编辑该区域。RNA 编辑受损dyf-5CAmRNA 剪接和由此产生的内含子保留阻止了 DYF-5CA 蛋白质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广泛的机制。