title: Loss of LIN-35, the Caenorhabditis elegans ortholog of the tumor suppressor p105Rb, results in enhanced RNA interference.
abstract: BACKGROUND
  Genome-wide RNA interference (RNAi) screening is a very powerful tool for analyzing gene function in vivo in Caenorhabditis elegans. The effectiveness of RNAi varies from gene to gene, however, and neuronally expressed genes are largely refractive to RNAi in wild-type worms.
  
  
  RESULTS
  We found that C. elegans strains carrying mutations in lin-35, the worm ortholog of the tumor suppressor gene p105Rb, or a subset of the genetically related synMuv B family of chromatin-modifying genes, show increased strength and penetrance for many germline, embryonic, and post-embryonic RNAi phenotypes, including neuronal RNAi phenotypes. Mutations in these same genes also enhance somatic transgene silencing via an RNAi-dependent mechanism. Two genes, mes-4 and zfp-1, are required both for the vulval lineage defects resulting from mutations in synMuv B genes and for RNAi, suggesting a common mechanism for the function of synMuv B genes in vulval development and in regulating RNAi. Enhanced RNAi in the germline of lin-35 worms suggests that misexpression of germline genes in somatic cells cannot alone account for the enhanced RNAi observed in this strain.
  
  
  CONCLUSIONS
  A worm strain with a null mutation in lin-35 is more sensitive to RNAi than any other previously described single mutant strain, and so will prove very useful for future genome-wide RNAi screens, particularly for identifying genes with neuronal functions. As lin-35 is the worm ortholog of the mammalian tumor suppressor gene p105Rb, misregulation of RNAi may be important during human oncogenesis.
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Lehner
authors.forename: Andrea
authors.initials: A
authors.lastname: Calixto
authors.forename: Catriona
authors.initials: C
authors.lastname: Crombie
authors.forename: Julia
authors.initials: J
authors.lastname: Tischler
authors.forename: Angelo
authors.initials: A
authors.lastname: Fortunato
authors.forename: Martin
authors.initials: M
authors.lastname: Chalfie
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Fraser
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019070:Cell Lineage; D020868:Gene Silencing; D017238:Genes, Helminth; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics; D009420:Nervous System / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000737:chemistry*; D013489:Suppression, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; C116485:lin-35 protein, C elegans