The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans

BJ Reinhart, FJ Slack, M Basson, AE Pasquinelli… - nature, 2000 - nature.com
BJ Reinhart, FJ Slack, M Basson, AE Pasquinelli, JC Bettinger, AE Rougvie, HR Horvitz…
nature, 2000nature.com
The C. elegans heterochronic gene pathway consists of a cascade of regulatory genes that
are temporally controlled to specify the timing of developmental events. Mutations in
heterochronic genes cause temporal transformations in cell fates in which stage-specific
events are omitted or reiterated. Here we show that let-7 is a heterochronic switch gene.
Loss of let-7 gene activity causes reiteration of larval cell fates during the adult stage,
whereas increased let-7 gene dosage causes precocious expression of adult fates during …
Abstract
The C. elegans heterochronic gene pathway consists of a cascade of regulatory genes that are temporally controlled to specify the timing of developmental events. Mutations in heterochronic genes cause temporal transformations in cell fates in which stage-specific events are omitted or reiterated. Here we show that let-7 is a heterochronic switch gene. Loss of let-7 gene activity causes reiteration of larval cell fates during the adult stage, whereas increased let-7 gene dosage causes precocious expression of adult fates during larval stages. let-7 encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3′ untranslated regions of the heterochronic genes lin-14, lin-28, lin-41, lin-42 and daf-12, indicating that expression of these genes may be directly controlled by let-7. A reporter gene bearing the lin-41 3′ untranslated region is temporally regulated in a let-7-dependent manner. A second regulatory RNA, lin-4, negatively regulates lin-14 and lin-28 through RNA–RNA interactions with their 3′ untranslated regions,. We propose that the sequential stage-specific expression of the lin-4 and let-7 regulatory RNAs triggers transitions in the complement of heterochronic regulatory proteins to coordinate developmental timing.
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