piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans germline

Cell. 2012 Jul 6;150(1):65-77. doi: 10.1016/j.cell.2012.06.015. Epub 2012 Jun 25.


Organisms employ a fascinating array of strategies to silence invasive nucleic acids such as transposons and viruses. Although evidence exists for several pathways that detect foreign sequences, including pathways that sense copy number, unpaired DNA, or aberrant RNA (e.g., dsRNA), in many cases, the mechanisms used to distinguish "self" from "nonself" nucleic acids remain mysterious. Here, we describe an RNA-induced epigenetic silencing pathway that permanently silences single-copy transgenes. We show that the Piwi Argonaute PRG-1 and its genomically encoded piRNA cofactors initiate permanent silencing, and maintenance depends on chromatin factors and the WAGO Argonaute pathway. Our findings support a model in which PRG-1 scans for foreign sequences and two other Argonaute pathways serve as epigenetic memories of "self" and "nonself" RNAs. These findings suggest how organisms can utilize RNAi-related mechanisms to detect foreign sequences not by any molecular signature, but by comparing the foreign sequence to a memory of previous gene expression.

Publication types

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

MeSH terms

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


  • Argonaute Proteins
  • Caenorhabditis elegans Proteins
  • PRG-1 protein, C elegans
  • RNA, Helminth
  • RNA, Small Interfering

Associated data

  • GEO/GSE38724