Abstract
The microRNA
let-7 is a critical regulator of developmental timing events at the larval-to-adult transition in
C.
elegans. Recently, microRNAs with sequence similarity to
let-7 have been identified. We find that doubly mutant animals lacking the
let-7 family microRNA genes
mir-48 and
mir-84 exhibit retarded molting behavior and retarded adult gene expression in the hypodermis. Triply mutant animals lacking
mir-48,
mir-84, and
mir-241 exhibit repetition of L2-stage events in addition to retarded adult-stage events.
mir-48,
mir-84, and
mir-241 function together to control the L2-to-L3 transition, likely by base pairing to complementary sites in the
hbl-1 3′ UTR and downregulating
hbl-1 activity. Genetic analysis indicates that
mir-48,
mir-84, and
mir-241 specify the timing of the L2-to-L3 transition in parallel to the heterochronic genes
lin-28 and
lin-46. These results indicate that
let-7 family microRNAs function in combination to affect both early and late developmental timing decisions.