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

Brenda J. Reinhart, Frank J. Slack, Michael Basson, Amy E. Pasquinelli, Jill C. Bettinger, Ann E. Rougvie, H. Robert Horvitz and Gary Ruvkun
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Brenda J. Reinhart: Harvard Medical School
Frank J. Slack: Harvard Medical School
Michael Basson: Massachusetts Institute of Technology
Amy E. Pasquinelli: Harvard Medical School
Jill C. Bettinger: Axys Pharmaceuticals
Ann E. Rougvie: Cell Biology and Development, University of Minnesota, St Paul
H. Robert Horvitz: Massachusetts Institute of Technology
Gary Ruvkun: Harvard Medical School

Nature, 2000, vol. 403, issue 6772, 901-906

Abstract: Abstract The C. elegans heterochronic gene pathway consists of a cascade of regulatory genes that are temporally controlled to specify the timing of developmental events1. Mutations in heterochronic genes cause temporal transformations in cell fates in which stage-specific events are omitted or reiterated2. 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 regions3,4. 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.

Date: 2000
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DOI: 10.1038/35002607

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