Control of developmental timing by small temporal RNAs: a paradigm for RNA-mediated regulation of gene expression

Bioessays. 2002 Feb;24(2):119-29. doi: 10.1002/bies.10046.


Heterochronic genes control the timing of developmental programs. In C. elegans, two key genes in the heterochronic pathway, lin-4 and let-7, encode small temporally expressed RNAs (stRNAs) that are not translated into protein. These stRNAs exert negative post-transcriptional regulation by binding to complementary sequences in the 3' untranslated regions of their target genes. stRNAs are transcribed as longer precursor RNAs that are processed by the RNase Dicer/DCR-1 and members of the RDE-1/AGO1 family of proteins, which are better known for their roles in RNA interference (RNAi). However, stRNA function appears unrelated to RNAi. Both sequence and temporal regulation of let-7 stRNA is conserved in other animal species suggesting that this is an evolutionarily ancient gene. Indeed, C. elegans, Drosophila and humans encode at least 86 other RNAs with similar structural features to lin-4 and let-7. We postulate that other small non-coding RNAs may function as stRNAs to control temporal identity during development in C. elegans and other organisms.

Publication types

  • Review

MeSH terms

  • 3' Untranslated Regions / genetics*
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Lineage
  • Endoribonucleases / genetics
  • Gene Expression Regulation, Developmental*
  • Gene Silencing / physiology
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Humans
  • MicroRNAs
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Ribonuclease III


  • 3' Untranslated Regions
  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • MicroRNAs
  • RNA, Small Nuclear
  • Repressor Proteins
  • lin-4 microRNA, C elegans
  • Endoribonucleases
  • Ribonuclease III