Reprogramming of transcriptome after hormetic heat stress by the endoribonuclease ENDU‑2 improves lifespan and stress resistance in C. elegans

Abstract Any organism is constantly exposed to dangerous, potentially life-threatening environmental impacts that demand coordinated responses. Although acute stress responses as temporal reactions to unfavorable external or internal factors are well known, transient stress experiences may have long-term physiological consequences. The underlying mechanisms adjusting cellular activities across time scale is poorly understood. Here, we investigate the long-term alteration of C. elegans transcriptome after a short heat shock (HS) exposure and discovered that the canonical HS response is followed by a profound transcriptional reprogramming that affects many genes involved in innate immunity response. This transcriptional reprogramming depends on the function of the endoribonuclease ENDU-2 but not the heat shock factor 1 (HSF-1). ENDU-2 in this context co-localizes with chromatin and interacts with RNA polymerase Pol II to specifically regulate transcription in the post-HS period. Failure to activate this post-HS response does not impair survival of animals upon HS insult, but abolishes the hormetic HS mediated beneficial effects. In summary, our work discovers that the hormetic long-term effects of a transient HS are mediated by the RNA-binding protein ENDU-2 that determines aging and longevity.