CaltechAUTHORS
Published May 22, 2008 | Version Accepted Version + Supplemental Material
Journal Article Open

Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes

Creators

  • 1. ROR icon Cold Spring Harbor Laboratory
  • 2. ROR icon University of Pennsylvania
  • 3. ROR icon University of Oxford

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.

Additional Information

© 2008 Nature Publishing Group. Received 01 November 2007; Accepted 07 March 2008; Published 10 April 2008. We thank members of the Hannon laboratory for discussions. O.H.T. is a Bristol-Meyers Squibb fellow and A.G. is a Florence Gould Foundation Scholar of the Watson School of Biological Sciences. E.P.M. is supported by a fellowship from the Australian-American Association. This work was supported in part by grants from the NIH (R.M.S. and G.J.H.) and gifts from Kathryn W. Davis and the Stanley family (G.J.H. and E.H.). G.J.H. is an Investigator of the Howard Hughes Medical Institute. Oliver H. Tam & Alexei A. Aravin: These authors contributed equally to this work.

Attached Files

Accepted Version - nihms249583.pdf

Supplemental Material - nature06904-s1.pdf

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nature06904-s1.pdf

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Additional details

Identifiers

PMCID
PMC2981145
Eprint ID
95353
Resolver ID
CaltechAUTHORS:20190508-134616985

Funding

Bristol-Myers Squibb
Florence Gould Foundation
Australian-American Association
Kathryn W. Davis
Stanley Family
Howard Hughes Medical Institute (HHMI)

Dates

Created
2019-05-09
Created from EPrint's datestamp field
Updated
2021-11-16
Created from EPrint's last_modified field