Fig. 1: RNA editing as part of regulatory loops.

a RNA editing in feedforward control. In endothelial cells, stress induces CTSB S-nitrosylation, which induces ADD1 dephosphorylation and translocation to the nucleus. An uncharacterized, likely also stress-induced factor X, may join ADD1 to form a complex with MATR3, which in turn recruits ADAR1 and targets the complex to CTSB mRNA to catalyze RNA editing. The altered sequence binds HuR, leading to increased RNA stability to enhance CTSB translation. b RNA editing in feedback control to maintain ciliary homeostasis in worm. The ciliary kinase DYF-5 becomes activated by phosphorylation, and through an unknown mechanism, such activated kinase induces antisense transcription within the kinase gene, leading to the formation of dsRNA that recruits ADR-2 to edit its own pre-mRNA. Some critical splicing signals are impaired to cause intron retention, thereby triggering nonsense-mediated mRNA decay to limit DYF-5 translation. Interestingly, hyperactivated DYF-5 also induces antisense transcription to limit the expression of the other two ciliary kinases, indicating a coordinated feedback control program to prevent ciliopathies in worm.