C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts

Cell. 2012 Jul 6;150(1):78-87. doi: 10.1016/j.cell.2012.06.016. Epub 2012 Jun 25.


Piwi Argonautes and Piwi-interacting RNAs (piRNAs) mediate genome defense by targeting transposons. However, many piRNA species lack obvious sequence complementarity to transposons or other loci; only one C. elegans transposon is a known piRNA target. Here, we show that, in mutants lacking the Piwi Argonaute PRG-1 (and consequently its associated piRNAs/21U-RNAs), many silent loci in the germline exhibit increased levels of mRNA expression with a concomitant depletion of RNA-dependent RNA polymerase (RdRP)-derived secondary small RNAs termed 22G-RNAs. Sequences depleted of 22G-RNAs are proximal to potential target sites that base pair imperfectly but extensively to 21U-RNAs. We show that PRG-1 is required to initiate, but not to maintain, silencing of transgenes engineered to contain complementarity to endogenous 21U-RNAs. Our findings support a model in which C. elegans piRNAs utilize their enormous repertoire of targeting capacity to scan the germline transcriptome for foreign sequences, while endogenous germline-expressed genes are actively protected from piRNA-induced silencing.

Publication types

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

MeSH terms

  • Animals
  • Argonaute Proteins / metabolism
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Gene Silencing
  • Genome, Helminth*
  • Germ Cells
  • RNA, Helminth / metabolism*
  • RNA, Small Interfering / metabolism*


  • Argonaute Proteins
  • RNA, Helminth
  • RNA, Small Interfering

Associated data

  • GEO/GSE38723