RRC ID 59492
Author Ganem NS, Ben-Asher N, Manning AC, Deffit SN, Washburn MC, Wheeler EC, Yeo GW, Zgayer OB, Mantsur E, Hundley HA, Lamm AT.
Title Disruption in A-to-I Editing Levels Affects C. elegans Development More Than a Complete Lack of Editing.
Journal Cell Rep
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.
Volume 27(4)
Pages 1244-1253.e4
Published 2019-4-23
DOI 10.1016/j.celrep.2019.03.095
PII S2211-1247(19)30434-6
PMID 31018137
PMC PMC8139731
MeSH Adenosine / genetics* Adenosine Deaminase / genetics Adenosine Deaminase / metabolism* Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Inosine / genetics* Mutation Phenotype Proteome / analysis RNA Editing* Transcriptome
IF 7.815
Times Cited 2
Resource
C.elegans tm668