Cell Reports, 23 April 2019, Vol.27(4), pp.1244-1253.e4
A-to-I RNA editing, catalyzed by ADAR proteins, is widespread in eukaryotic transcriptomes. Studies showed that, in , 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. Ganem et al. report that the 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.
Adar ; C. elegans ; Gene Expression ; Transcriptomics ; Organism Development ; Biology
View record in ScienceDirect (Access to full text may be restricted)
View full text in ScienceDirect