RNA interference links oxidative stress to the inhibition of heat stress adaptation.

Increased oxidative stress is associated with various diseases and aging, while adaptation to heat stress is an important determinant of survival and contributes to longevity. However, the impact of oxidative stress on heat resistance remains largely unclear. Aim: In this study we investigated how oxidative stress impinges on heat stress responses. Results: We report that hydrogen-peroxide (H2O2) pretreatment inhibits both acquired thermotolerance and heat-induced Hsp70 expression in mammalian cells, as well as acquired thermotolerance in the nematode Caenorhabditis elegans, via RNA interference. Moreover, we demonstrate that elimination of RNA interference by silencing key enzymes in microRNA biogenesis, dcr-1 or pash-1, restores the diminished intrinsic thermotolerance of aged and H2O2-elimination compromised (catalase-2 and peroxiredoxin-2 deficient) worms. Innovation and Conclusion: These results uncover a novel post-transcriptional element in the regulation of heat stress adaptation under oxidative conditions that may have implications in disease susceptibility and aging. Antioxid. Redox Signal. 17, 890-901.