Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations

Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):E4323-31. doi: 10.1073/pnas.1406131111. Epub 2014 Sep 25.


Germ cells are maintained in a pristine non-aging state as they proliferate over generations. Here, we show that a novel function of the Caenorhabditis elegans RNA interference proteins RNAi spreading defective (RSD)-2 and RSD-6 is to promote germ cell immortality at high temperature. rsd mutants cultured at high temperatures became progressively sterile and displayed loss of small interfering RNAs (siRNAs) that target spermatogenesis genes, simple repeats, and transposons. Desilencing of spermatogenesis genes occurred in late-generation rsd mutants, although defective spermatogenesis was insufficient to explain the majority of sterility. Increased expression of repetitive loci occurred in both germ and somatic cells of late-generation rsd mutant adults, suggesting that desilencing of many heterochromatic segments of the genome contributes to sterility. Nuclear RNAi defective (NRDE)-2 promotes nuclear silencing in response to exogenous double-stranded RNA, and our data imply that RSD-2, RSD-6, and NRDE-2 function in a common transgenerational nuclear silencing pathway that responds to endogenous siRNAs. We propose that RSD-2 and RSD-6 promote germ cell immortality at stressful temperatures by maintaining transgenerational epigenetic inheritance of endogenous siRNA populations that promote genome silencing.

Keywords: fertility; germ line; tudor domain protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Line, Transformed
  • Cell Proliferation
  • Chromosome Segregation
  • Gene Expression Regulation
  • Gene Silencing
  • Genetic Loci
  • Germ Cells / cytology*
  • Germ Cells / metabolism*
  • Infertility
  • Mutation
  • Nondisjunction, Genetic
  • RNA, Small Interfering / metabolism*
  • Spermatogenesis
  • Stress, Physiological
  • Tandem Repeat Sequences / genetics
  • Temperature
  • Transcription, Genetic


  • Caenorhabditis elegans Proteins
  • RNA, Small Interfering
  • RSD-2 protein, C elegans
  • RSD-6 protein, C elegans

Associated data

  • GEO/GSE40460