Open AccessRegulation of RNA editing by intracellular acidification
Author(s) -
Turnee N Malik,
Erin E Doherty,
Vandana Gaded,
Theodore M. Hill,
Peter A. Beal,
Ronald B. Emeson
Publication year - 2021
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gkab157
Subject(s) - adar , rna editing , biology , rna , rna silencing , adenosine deaminase , deamination , biochemistry , rna binding protein , microbiology and biotechnology , inosine , rna interference , adenosine , enzyme , gene
The hydrolytic deamination of adenosine-to-inosine (A-to-I) by RNA editing is a widespread post-transcriptional modification catalyzed by the adenosine deaminase acting on RNA (ADAR) family of proteins. ADAR-mediated RNA editing modulates cellular pathways involved in innate immunity, RNA splicing, RNA interference, and protein recoding, and has been investigated as a strategy for therapeutic intervention of genetic disorders. Despite advances in basic and translational research, the mechanisms regulating RNA editing are poorly understood. Though several trans-acting regulators of editing have been shown to modulate ADAR protein expression, previous studies have not identified factors that modulate ADAR catalytic activity. Here, we show that RNA editing increases upon intracellular acidification, and that these effects are predominantly explained by both enhanced ADAR base-flipping and deamination rate at acidic pH. We also show that the extent of RNA editing increases with the reduction in pH associated with conditions of cellular hypoxia.