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26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans.

Endogenous small interfering RNAs (endo-siRNAs) regulate diverse gene expression programs in eukaryotes by either binding and cleaving mRNA targets or mediating heterochromatin formation; however, the mechanisms of endo-siRNA biogenesis, sorting, and target regulation remain poorly understood. Here we report the identification and function of a specific class of germline-generated endo-siRNAs in Caenorhabditis elegans that are 26 nt in length and contain a guanine at the first nucleotide position (i.e., 26G RNAs). 26G RNAs regulate gene expression during spermatogenesis and zygotic development, and their biogenesis requires the ERI-1 exonuclease and the RRF-3 RNA-dependent RNA polymerase (RdRP). Remarkably, we identified two nonoverlapping subclasses of 26G RNAs that sort into specific RNA-induced silencing complexes (RISCs) and differentially regulate distinct mRNA targets. Class I 26G RNAs target genes are expressed during spermatogenesis, whereas class II 26G RNAs are maternally inherited and silence gene expression during zygotic development. These findings implicate a class of endo-siRNAs in the global regulation of transcriptional programs required for fertility and development.

Pubmed ID: 19846761


  • Han T
  • Manoharan AP
  • Harkins TT
  • Bouffard P
  • Fitzpatrick C
  • Chu DS
  • Thierry-Mieg D
  • Thierry-Mieg J
  • Kim JK


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

November 3, 2009

Associated Grants

  • Agency: NHGRI NIH HHS, Id: HG004276-01
  • Agency: NIGMS NIH HHS, Id: S06 GM52588
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Exoribonucleases
  • Gene Expression Regulation, Developmental
  • Gene Silencing
  • Germ Cells
  • Guanine
  • Male
  • RNA, Helminth
  • RNA, Small Interfering
  • Sequence Analysis, DNA
  • Spermatogenesis
  • Zygote