To "Z" or not to "Z": Z-RNA, self-recognition, and the MDA5 helicase.

ABSTRACT: Double-stranded RNA (dsRNA) is produced both by virus and host. Its recognition by the melanoma differentiation-associated gene 5 (MDA5) initiates type I interferon responses. How can a host distinguish self-transcripts from nonself to ensure that responses are targeted correctly? Here, I discuss a role for MDA5 helicase in inducing Z-RNA formation by Alu inverted repeat (AIR) elements. These retroelements have highly conserved sequences that favor Z-formation, creating a site for the dsRNA-specific deaminase enzyme ADAR1 to dock. The subsequent editing destabilizes the dsRNA, ending further interaction with MDA5 and terminating innate immune responses directed against self. By enabling self-recognition, Alu retrotransposons, once invaders, now are genetic elements that keep immune respons

SUBMITTER: Herbert A 

PROVIDER: S-EPMC8118290 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature