Disruption in A-to-I Editing Levels Affects C. elegans Development More Than a Complete Lack of Editing
| Autor: | Nabeel S. Ganem, Aidan C. Manning, Einav Mantsur, Emily C. Wheeler, Ayelet T. Lamm, Noa Ben-Asher, Orna Ben-Naim Zgayer, Heather A. Hundley, Michael C. Washburn, Sarah N. Deffit, Gene W. Yeo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adenosine Proteome Adenosine Deaminase Mutant Biology General Biochemistry Genetics and Molecular Biology Article Transcriptome 03 medical and health sciences 0302 clinical medicine Gene expression Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Gene 030304 developmental biology Genetics 0303 health sciences RNA Phenotype Inosine Cell biology RNA silencing 030104 developmental biology RNA editing ADAR Mutation RNA Editing 030217 neurology & neurosurgery |
| Zdroj: | Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY A-to-I RNA editing, catalyzed by ADAR proteins, is widespread in eukaryotic transcriptomes. Studies showed that, in C. elegans, ADR-2 can actively deaminate dsRNA, whereas ADR-1 cannot. Therefore, we set out to study the effect of each of the ADAR genes on the RNA editing process. We performed comprehensive phenotypic, transcriptomics, proteomics, and RNA binding screens on worms mutated in a single ADAR gene. We found that ADR-1 mutants exhibit more-severe phenotypes than ADR-2, and some of them are a result of non-editing functions of ADR-1. We also show that ADR-1 significantly binds edited genes and regulates mRNA expression, whereas the effect on protein levels is minor. In addition, ADR-1 primarily promotes editing by ADR-2 at the L4 stage of development. Our results suggest that ADR-1 has a significant role in the RNA editing process and in altering editing levels that affect RNA expression; loss of ADR-1 results in severe phenotypes. Graphical Abstract In Brief Ganem et al. report that the C. elegans enzymatic-inactive ADR-1 regulates A-to-I RNA editing by directing editing by ADR-2, mainly at the L4 developmental stage. Changes in RNA editing levels severely affect normal development by changing RNA levels, but not protein levels. |
| Databáze: | OpenAIRE |
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