Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans

Abstract

During C. elegans development, the temporal pattern of many cell lineages is specified by graded activity of the heterochronic gene Lin-14. Here we demonstrate that a temporal gradient in Lin-14 protein is generated posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and sufficient to confer lin-4-mediated posttranscriptional temporal regulation. The function of the lin-14 3'UTR is conserved between C. elegans and C. briggsae. Among the conserved sequences are seven elements that are each complementary to the lin-4 RNAs. A reporter gene bearing three of these elements shows partial temporal gradient activity. These data suggest a molecular mechanism for Lin-14p temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation.

Principles of micro-RNA production and maturation

“…When Ambros, Ruvkun and colleagues reported the cloning and functional analysis of the first micro-RNA (miRNA), lin-4, in 1993, they also provided a glimpse of things to come on the mechanism of miRNA production (Lee et al, 1993;Wightman et al, 1993). The authors demonstrated that there existed two RNA species, the 22-nucleotide (nt) lin-4S and the less abundant, approximately 60 nt lin-4L.…”

Les microARN circulants, une nouvelle classe de biomarqueurs pour la médecine

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