Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants

Nature. 2005 Jul 28;436(7050):593-7. doi: 10.1038/nature04010.

Abstract

Caenorhabditis elegans homologues of the retinoblastoma (Rb) tumour suppressor complex specify cell lineage during development. Here we show that mutations in Rb pathway components enhance RNA interference (RNAi) and cause somatic cells to express genes and elaborate perinuclear structures normally limited to germline-specific P granules. Furthermore, particular gene inactivations that disrupt RNAi reverse the cell lineage transformations of Rb pathway mutants. These findings suggest that mutations in Rb pathway components cause cells to revert to patterns of gene expression normally restricted to germ cells. Rb may act by a similar mechanism to transform mammalian cells.

MeSH terms

  • Alleles
  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cytoplasmic Granules / metabolism*
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Helminth / genetics
  • Germ Cells / cytology*
  • Germ Cells / metabolism*
  • Mutation / genetics*
  • Phenotype
  • RNA Interference*
  • RNA-Dependent RNA Polymerase / genetics
  • RNA-Dependent RNA Polymerase / metabolism
  • Retinoblastoma / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transgenes / genetics
  • Vulva / cytology
  • Vulva / metabolism
  • Vulva / pathology

Substances

  • Caenorhabditis elegans Proteins
  • Transcription Factors
  • lin-15B protein, C elegans
  • RNA-Dependent RNA Polymerase
  • RNA-directed RNA polymerase RRF-3, C elegans
  • ERI-1 protein, C elegans
  • Exoribonucleases