The
mir-51 family of microRNAs (miRNAs) in C. elegans are part of the deeply conserved miR-99/100 family. While loss of all six family members (
mir-51-56) in C. elegans results in embryonic lethality, loss of individual
mir-51 family members results in a suppression of retarded developmental timing defects associated with the loss of
alg-1. The mechanism of this suppression of developmental timing defects is unknown. To address this, we characterized the function of the
mir-51 family in the developmental timing pathway. We performed genetic analysis and determined that
mir-51 family members regulate the developmental timing pathway in the L2 stage upstream of
hbl-1. Loss of the
mir-51 family member,
mir-52, suppressed retarded developmental timing defects associated with the loss of
let-7 family members and
lin-46. Enhancement of precocious defects was observed for mutations in
lin-14,
hbl-1, and
mir-48(
ve33), but not later acting developmental timing genes. Interestingly,
mir-51 family members showed genetic interactions with additional miRNA-regulated pathways, which are regulated by the
let-7 and
mir-35 family miRNAs,
lsy-6, miR-240/786, and miR-1. Loss of
mir-52 likely does not suppress miRNA-regulated pathways through an increase in miRNA biogenesis or miRNA activity. We found no increase in the levels of four mature miRNAs,
let-7, miR-58, miR-62 or miR-244, in
mir-52 or
mir-52/53/54/55/56 mutant worms. In addition, we observed no increase in the activity of ectopic
lsy-6 in the repression of a downstream target in uterine cells in worms that lack
mir-52. We propose that the
mir-51 family functions broadly through the regulation of multiple targets, which have not yet been identified, in diverse regulatory pathways in C. elegans.