The majority of A-to-I RNA editing is not required for mammalian homeostasis

71Citations
Citations of this article
91Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Background: Adenosine-to-inosine (A-to-I) RNA editing, mediated by ADAR1 and ADAR2, occurs at tens of thousands to millions of sites across mammalian transcriptomes. A-to-I editing can change the protein coding potential of a transcript and alter RNA splicing, miRNA biology, RNA secondary structure and formation of other RNA species. In vivo, the editing-dependent protein recoding of GRIA2 is the essential function of ADAR2, while ADAR1 editing prevents innate immune sensing of endogenous RNAs by MDA5 in both human and mouse. However, a significant proportion of A-to-I editing sites can be edited by both ADAR1 and ADAR2, particularly within the brain where both are highly expressed. The physiological function(s) of these shared sites, including those evolutionarily conserved, is largely unknown. Results: To generate completely A-to-I editing-deficient mammals, we crossed the viable rescued ADAR1-editing-deficient animals (Adar1 E861A/E861A Ifih1 -/- ) with rescued ADAR2-deficient (Adarb1 -/- Gria2 R/R ) animals. Unexpectedly, the global absence of editing was well tolerated. Adar1 E861A/E861A Ifih1 -/- Adarb1 -/- Gria2 R/R were recovered at Mendelian ratios and age normally. Detailed transcriptome analysis demonstrated that editing was absent in the brains of the compound mutants and that ADAR1 and ADAR2 have similar editing site preferences and patterns. Conclusions: We conclude that ADAR1 and ADAR2 are non-redundant and do not compensate for each other's essential functions in vivo. Physiologically essential A-to-I editing comprises a small subset of the editome, and the majority of editing is dispensable for mammalian homeostasis. Moreover, in vivo biologically essential protein recoding mediated by A-to-I editing is an exception in mammals.

Cite

CITATION STYLE

APA

Chalk, A. M., Taylor, S., Heraud-Farlow, J. E., & Walkley, C. R. (2019). The majority of A-to-I RNA editing is not required for mammalian homeostasis. Genome Biology, 20(1). https://doi.org/10.1186/s13059-019-1873-2

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free