1. Disruption in A-to-I Editing Levels Affects C. elegans Development More Than a Complete Lack of Editing.
- Author
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Ganem NS, Ben-Asher N, Manning AC, Deffit SN, Washburn MC, Wheeler EC, Yeo GW, Zgayer OB, Mantsur E, Hundley HA, and Lamm AT
- Subjects
- Adenosine Deaminase genetics, Animals, Caenorhabditis elegans genetics, Caenorhabditis elegans metabolism, Caenorhabditis elegans Proteins genetics, Mutation, Phenotype, Proteome analysis, Transcriptome, Adenosine genetics, Adenosine Deaminase metabolism, Caenorhabditis elegans growth & development, Caenorhabditis elegans Proteins metabolism, Inosine genetics, RNA Editing
- Abstract
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., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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