Small regulatory RNA pathways play essential, conserved roles in diverse biological processes, including in development, cellular differentiation, germline integrity, and viral defense. While fundamental insights into the mechanisms of small RNA biogenesis and gene silencing have been made, the interplay between functionally distinct small RNA pathways, some of which share common factors, remains incompletely understood. We have discovered that the conserved serine/threonine kinase SGK-1 genetically interacts with both the microRNA (miRNA) and small interfering RNA (siRNA) pathways in an opposing fashion. Loss of
sgk-1 suppresses
let-7 miRNA mutant defects and attenuates the potency of feeding RNAi, which silences targets via siRNAs. Loss of
sgk-1 also promotes the accumulation of mature
let-7 and silencing of the
let-7 target,
lin-41 mRNA, in a
let-7 hypomorphic mutant. Likewise,
sgk-1 gain-of-function mutants enhance miRNA mutant defects and enhance the efficacy of feeding RNAi. We hypothesize that SGK-1 kinase activity acts to "balance" miRNA and siRNA functions. SGK-1 is orthologous to the mammalian Serum and Glucocorticoid-inducible Kinases (SGKs) and has conserved roles in mediating metabolism, growth, and cellular stress responses downstream of TOR and insulin signaling pathways. Interestingly, we observe that loss of
rict-1, which encodes the TORC2 component Rictor, also suppresses a
let-7 miRNA mutant defect, suggesting that SGK-1 function in small RNA pathways may be mediated through TORC2. Our data suggest that SGK-1 may directly interact with components of the miRNA-Induced Silencing Complex (miRISC). In silico analysis also revealed SGK-1 phosphorylation motifs in factors of both pathways. Our current research is focused on (A) defining the mechanism by which
sgk-1 differentially affects the miRNA and siRNA pathways, including exploring if protein(s) in these pathways are direct SGK-1 substrates, and (B) investigating if SGK-1 impact on small RNA pathways is regulated by conserved energy and stress sensing pathways.