Pseudogene-derived Small Interfering RNAs Regulate Gene Expression in Mouse Oocytes

Nature. 2008 May 22;453(7194):534-8. doi: 10.1038/nature06904. Epub 2008 Apr 10.

Abstract

Pseudogenes populate the mammalian genome as remnants of artefactual incorporation of coding messenger RNAs into transposon pathways. Here we show that a subset of pseudogenes generates endogenous small interfering RNAs (endo-siRNAs) in mouse oocytes. These endo-siRNAs are often processed from double-stranded RNAs formed by hybridization of spliced transcripts from protein-coding genes to antisense transcripts from homologous pseudogenes. An inverted repeat pseudogene can also generate abundant small RNAs directly. A second class of endo-siRNAs may enforce repression of mobile genetic elements, acting together with Piwi-interacting RNAs. Loss of Dicer, a protein integral to small RNA production, increases expression of endo-siRNA targets, demonstrating their regulatory activity. Our findings indicate a function for pseudogenes in regulating gene expression by means of the RNA interference pathway and may, in part, explain the evolutionary pressure to conserve argonaute-mediated catalysis in mammals.

Publication types

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

MeSH terms

  • Animals
  • Computational Biology
  • DNA Transposable Elements / genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Gene Library
  • Mice
  • Oocytes / metabolism*
  • Pseudogenes / genetics*
  • RNA Interference*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics*
  • Ribonuclease III / deficiency
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism

Substances

  • DNA Transposable Elements
  • RNA, Messenger
  • RNA, Small Interfering
  • Ribonuclease III