Misexpression of the Caenorhabditis elegans miRNA let-7 is sufficient to drive developmental programs

Cold Spring Harb Symp Quant Biol. 2006:71:21-7. doi: 10.1101/sqb.2006.71.018.

Abstract

The Caenorhabditis elegans microRNAs (miRNAs) lin-4 and let-7 promote transitions between stage-specific events in development by down-regulating the translation of their target genes. Expression of let-7 is required at the fourth larval stage for the proper transition from larval to differentiated, adult fates in the hypodermis; however, it was not known whether expression of let-7 is sufficient to specify these adult fates. To test this, we created fusion genes between lin-4 and let-7 that direct the expression of let-7 two stages early, at the L2 stage. We find that animals bearing the fusion genes show precocious adult development at the L4 stage, indicating that temporal misexpression of let-7 is sufficient to direct the larval-to-adult transition. Additionally, an RNA interference (RNAi)-based screen for enhancers of the precocious phenotype identified the period ortholog lin-42, among other genes, which are candidate modulators of the effects of let-7 expression. let-7 is conserved throughout bilaterian phylogeny, and orthologs of its targets have roles in vertebrate development, suggesting the importance of understanding how let-7 promotes terminal differentiation in C. elegans and other organisms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development*
  • Caenorhabditis elegans Proteins / genetics
  • DNA-Binding Proteins / genetics
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental
  • Gene Fusion
  • MicroRNAs / genetics*
  • Phenotype
  • Promoter Regions, Genetic
  • RNA, Helminth / genetics*
  • Transcription Factors / genetics

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • LIN-29 protein, C elegans
  • MicroRNAs
  • RNA, Helminth
  • Transcription Factors
  • let-7 microRNA, C elegans
  • lin-4 microRNA, C elegans