The heterochronic pathway controls the temporal progression of C. elegans development by temporally regulating the abundance or activities of a succession of heterochronic genes.
lin-41 null mutant animals precociously express adult characteristics at earlier larval stages. In contrast, overexpression of
lin-41 causes a retarded phenotype: some cells reiterate late larval fates at the adult stage. Thus
lin-41 is necessary and sufficient for the delay of adult-specific fates during earlier larval stages.
lin-41 negatively regulates the expression of
lin-29 , a transcription factor required for adult fates.
lin-29 is translated at the L4 and adult stages from an mRNA expressed from the L2 stage. In a
lin-41 mutant, LIN-29 protein appears as early as the L2 stage. Thus LIN-41 may regulate the timing of
lin-29 mRNA translation.
lin-41 is alternatively spliced and encodes two members of the RBCC (RING finger, B-Box, Coiled coil) family, a diverse family of regulatory proteins, that includes the RNA binding protein SSA/Ro.
lin-41 is widely expressed. In the hypodermis its expression is down-regulated during the L4 stage, which is when translation of the
lin-29 mRNA is initiated. A fusion of GFP to a functional LIN-41 protein reveals that the protein is predominantly cytoplasmic. Based on precedents from the RBCC gene family, LIN-41 may regulate
lin-29 expression by binding to the mRNA to control its translation. We isolated
lin-41 mutations as suppressors of
let-7 mutations.
let-7 encodes a small untranslated RNA that is expressed at the L3 and later stages (B. Reinhart, personnel communication) and is complementary to two sites in the 3'UTR of
lin-41 . This complementarity and the temporal regulation of
lin-41 expression at the time when
let-7 RNA is up-regulated suggests that
let-7 inhibits
lin-41 expression by binding to the 3' UTR. Thus activation of the
let-7 regulatory RNA during the L4 and adult stages may downregulate LIN-41 expression to then relieve the translational inhibition of the
lin-29 mRNA. In this way,
lin-41 may transduce temporal information from a regulatory RNA to a transcriptional output.