AMPK tunes reproductive gene expression and small RNA homeostasis to mediate timely germ cell development

Developmental plasticity allows organisms to adapt to environmental stressors and improve fitness. Caenorhabditis elegans can enter an alternative larval stage, the dauer, marked by developmental quiescence and complete transcriptomic remodeling. The energy modulator AMPK is required for animals to passage through dauer while preserving germline quiescence. Without AMPK, dauer animals exhibit reproductive defects, which are partially suppressed by disabling small RNA pathway components. To understand how the loss of AMPK affects RNA homeostasis and gene expression, we performed transcriptomic analysis of AMPK mutants. We reveal that over 60% of the C. elegans genes are affected by the loss of AMPK during the dauer stage. This is accompanied by a widespread increase in reproductive gene expression in dauer, as well as the upregulation of most small RNAs and small RNA pathway components, particularly the spermatogenic Argonautes ALG-3/4. Eliminating ALG-3/4 corrects several reproductive defects, including premature dauer spermatogenesis, and partially restores fertility. Notably, decreasing global small RNA biogenesis also partially corrects these phenotypes, possibly by destabilizing their associated Argonaute effectors. Our work highlights a role for AMPK in the temporal regulation of small RNA populations to establish a delicate balance that is essential for reproductive fitness following quiescence during periods of stress.