RNAi-mediated regulation of alg-3 and alg-4 coordinates the spermatogenesis developmental program in C. elegans

Coordination of gene regulatory networks is necessary for proper execution of cellular programs throughout development. In C. elegans, spermatogenesis and oogenesis occur during different life stages (L4 and adult, respectively) within the hermaphroditic germline tissue. Yet, it remains unclear how these developmental programs are robustly executed, particularly during stressful conditions. Here we show evolutionarily conserved RNA interference (RNAi) pathways act to restrict expression of spermatogenesis genes to the L4 stage. Our findings indicate a novel RNAi-mediated regulatory cascade is essential for properly coordinating the spermatogenesis developmental program, particularly during heat stress. This is achieved through RNAi-mediated genetic switches that regulate the expression of the Argonautes, ALG-3 and ALG-4, to control ALG-3/4 pathway function. Moreover, this work provides key insights into the different molecular mechanisms RNAi pathways employ to maintain both maternal and paternal germ cells reproductive potential, and further highlights the complexities and importance of RNAi-mediated gene regulation in development.