RNA editing restricts hyperactive ciliary kinases.
basic_science · Level V
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- Record sourced from PubMed, PMID 34446600.
- Also identified by DOI 10.1126/science.abd8971.
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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 <i>Caenorhabditis elegans</i> that disrupted sensory cilia. Genetic suppressor screens identified that mutations of ADR-2, an RNA adenosine deaminase, rescued ciliary phenotypes of <i>dyf-5CA</i> We found that <i>dyf-5CA</i> animals abnormally transcribed antisense RNAs that pair with <i>dyf-5CA</i> messenger RNA (mRNA) to form double-stranded RNA, recruiting ADR-2 to edit the region ectopically. RNA editing impaired <i>dyf-5CA</i> mRNA splicing, and the resultant intron retentions blocked DYF-5CA protein translation and activated nonsense-mediated <i>dyf-5CA</i> 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.
Medical subject headings
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Cilia
- Mitogen-Activated Protein Kinases
- RNA Editing