Systematic identification of A-to-I RNA editing in zebrafish development and adult organs.

Ilana Buchumenski,Lior Appelbaum,Erez Y Levanon,Jan Philipp Junker,Eli Eisenberg,Karoline Holler

doi:10.1093/nar/gkab247

Abstract

A-to-I RNA editing is a common post transcriptional mechanism, mediated by the Adenosine deaminase that acts on RNA (ADAR) enzymes, that increases transcript and protein diversity. The study of RNA editing is limited by the absence of editing maps for most model organisms, hindering the understanding of its impact on various physiological conditions. Here, we mapped the vertebrate developmental landscape of A-to-I RNA editing, and generated the first comprehensive atlas of editing sites in zebrafish. Tens of thousands unique editing events and 149 coding sites were identified with high-accuracy. Some of these edited sites are conserved between zebrafish and humans. Sequence analysis of RNA over seven developmental stages revealed high levels of editing activity in early stages of embryogenesis, when embryos rely on maternal mRNAs and proteins. In contrast to the other organisms studied so far, the highest levels of editing were detected in the zebrafish ovary and testes. This resource can serve as the basis for understanding of the role of editing during zebrafish development and maturity.

Highlights

Adenosine to inosine (A-to-I) RNA editing is a posttranscriptional modification that diversifies the RNA sequence from the genomic DNA template
Recent evidence indicates that ADAR1 is critical for normal development in mammals [7,8], the lethal embryonic phenotype can be rescued by deletion of the double-strand RNA (dsRNA) sensor melanoma differentiation-associated protein 5 (MDA5) [9]
This observation led to the notion that the main role of ADAR1 is to edit target molecules in order to prevent mistaken identification of endogenous long double-stranded RNAs by dsRNA sensors and consequent triggering of the innate immune response [9,10,11]

Summary

Introduction

Adenosine to inosine (A-to-I) RNA editing is a posttranscriptional modification that diversifies the RNA sequence from the genomic DNA template. Recent evidence indicates that ADAR1 is critical for normal development in mammals [7,8], the lethal embryonic phenotype can be rescued by deletion of the dsRNA sensor melanoma differentiation-associated protein 5 (MDA5) [9]. This observation led to the notion that the main role of ADAR1 is to edit target molecules in order to prevent mistaken identification of endogenous long double-stranded RNAs by dsRNA sensors and consequent triggering of the innate immune response [9,10,11]

Methods

Results

Conclusion