RNA editing restricts hyperactive ciliary kinases

doi:10.1126/science.abd8971

GSTDTAP > 气候变化

DOI	10.1126/science.abd8971
	RNA editing restricts hyperactive ciliary kinases
	Dongdong Li; Yufan Liu; Peishan Yi; Zhiwen Zhu; Wei Li; Qiangfeng Cliff Zhang; Jin Billy Li; Guangshuo Ou
	2021-08-27
发表期刊	Science
出版年	2021
英文摘要	Ciliary kinases are essential for cilia formation and function but it remains unknown how their activities are regulated in vivo. Li et al. created roundworm animal models carrying hyperactive ciliary kinases that disrupt cilia. Their genetic suppressor screens revealed that loss of an RNA adenosine deaminase that catalyzes adenosine-to-inosine (A-to-I) RNA editing rescued ciliary abnormalities. They found that kinase hyperactivation caused this RNA adenosine deaminase to edit kinase RNA and impair kinase RNA splicing and translation, thereby downregulating ciliary kinases from nuclei. These results suggest that ciliopathies may be treated by targeting the pathways outside of cilia. Science , abd8971, this issue p. [984][1] 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. [1]: /lookup/doi/10.1126/science.abd8971
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/336657
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Dongdong Li,Yufan Liu,Peishan Yi,et al. RNA editing restricts hyperactive ciliary kinases[J]. Science,2021.
APA	Dongdong Li.,Yufan Liu.,Peishan Yi.,Zhiwen Zhu.,Wei Li.,...&Guangshuo Ou.(2021).RNA editing restricts hyperactive ciliary kinases.Science.
MLA	Dongdong Li,et al."RNA editing restricts hyperactive ciliary kinases".Science (2021).