The 21-nucleotide let-7 RNA Regulates Developmental Timing in Caenorhabditis Elegans

Nature. 2000 Feb 24;403(6772):901-6. doi: 10.1038/35002607.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins*
  • DNA, Helminth
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Developmental
  • Genes, Helminth
  • Genes, Switch*
  • Molecular Sequence Data
  • Protein Biosynthesis
  • RNA, Helminth / genetics
  • RNA, Helminth / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / physiology*
  • Suppression, Genetic
  • Transcription Factors / genetics

Substances

  • Caenorhabditis elegans Proteins
  • DNA, Helminth
  • DNA-Binding Proteins
  • LIN-29 protein, C elegans
  • RNA, Helminth
  • RNA, Messenger
  • Transcription Factors