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Cell Rep. 2019 Apr 23;27(4):1244-1253.e4. doi: 10.1016/j.celrep.2019.03.095.

Disruption in A-to-I Editing Levels Affects C. elegans Development More Than a Complete Lack of Editing.

Author information

1
Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
2
Medical Sciences Program, Indiana University, Bloomington, IN 47405, USA.
3
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
4
Department of Cellular and Molecular Medicine, Stem Cell Program and Institute for Genomic Medicine, University of California, San Diego, San Diego, CA, USA.
5
Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel. Electronic address: ayeletla@technion.ac.il.

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.

KEYWORDS:

ADAR; C. elegans; gene expression; organism development; transcriptomics

PMID:
31018137
DOI:
10.1016/j.celrep.2019.03.095
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