ADAR1 downregulation by autophagy drives senescence independently of RNA editing by enhancing p16^INK4a levels.

ABSTRACT: Cellular senescence plays a causal role in ageing and, in mice, depletion of p16^INK4a-expressing senescent cells delays ageing-associated disorders^1,2. Adenosine deaminases acting on RNA (ADARs) are RNA-editing enzymes that are also implicated as important regulators of human ageing, and ADAR inactivation causes age-associated pathologies such as neurodegeneration in model organisms^3,4. However, the role, if any, of ADARs in cellular senescence is unknown. Here we show that ADAR1 is post-transcriptionally downregulated by autophagic degradation to promote senescence through p16^INK4a upregulation. The ADAR1 downregulation is sufficient to drive senescence in both in vitro and in vivo models. Senescence induced by ADAR1 downregulation is p16^IN

SUBMITTER: Hao X 

PROVIDER: S-EPMC9757154 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature