POSTTRANSCRIPTIONAL REGULATION OF THE HETEROCHRONIC GENE LIN-14 BY LIN-4 MEDIATES TEMPORAL PATTERN-FORMATION IN C-ELEGANS

During C. elegans development, the temporal pattern of many cell linea ges is specified by graded activity of the heterochronic gene Lin-14. Here we demonstrate that a temporal gradient in Lin-14 protein is gene rated posttranscriptionally by multiple elements in the lin-14 3'UTR t hat are regulated by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and sufficient to confer lin-4-mediated posttranscript ional temporal regulation. The function of the lin-14 3'UTR is conserv ed between C. elegans and C. briggsae. Among the conserved sequences a re seven elements that are each complementary to the lin-4 RNAs. A rep orter gene bearing three of these elements shows partial temporal grad ient activity. These data suggest a molecular mechanism for Lin-14p te mporal gradient formation: the lin-4 RNAs base pair to sites in the li n-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 tra nslation.