Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants.
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.
Wang
Duo
D
Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
Kennedy
Scott
S
Conte
Darryl
D
Kim
John K
JK
Gabel
Harrison W
HW
Kamath
Ravi S
RS
Mello
Craig C
CC
Ruvkun
Gary
G
D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000235:genetics; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D034622:RNA Interference; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics / Q000378:metabolism; D012175:Retinoblastoma / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014844:Vulva / Q000166:cytology / Q000378:metabolism / Q000473:pathology
D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors; C088819:lin-15B protein, C elegans; D012324:RNA-Dependent RNA Polymerase; C472756:RNA-directed RNA polymerase RRF-3, C elegans; C482202:ERI-1 protein, C elegans; D005095:Exoribonucleases