Abstract
Non-coding small RNAs and Argonaute proteins mediate conserved defenses against foreign genetic elements. C. elegans mutants in the insulin/IGF-1 signaling (IIS) have previously been shown to exhibit an enhanced response to exogenous RNAi. Here, we found that the loss of IIS via daf-2 enhances transgene silencing, which is reversed by knocking out daf-16 /foxO . Similarly, pals-22 mutants show enhanced RNAi and upregulation of antiviral RNAi pathway. daf-2 and pals-22 mutations exhibit additive effects, and loss of daf-16 restores transgene expression in daf-2 mutants but not in pals-22 mutants, suggesting that these genes act in parallel. RNAi gene expression in daf-2 mutants lacked a consistent pattern, suggesting IIS may regulate RNAi components via post-translational mechanisms.