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

Tam, Oliver H. and Aravin, Alexei A. and Stein, Paula and Girard, Angelique and Murchison, Elizabeth P. and Cheloufi, Sihem and Hodges, Emily and Anger, Martin and Sachidanandam, Ravi and Schultz, Richard M. and Hannon, Gregory J. (2008) Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature, 453 (7194). pp. 534-538. ISSN 0028-0836. PMCID PMC2981145.

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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.

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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.
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Bristol-Myers SquibbUNSPECIFIED
Florence Gould FoundationUNSPECIFIED
Australian-American AssociationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:7194
PubMed Central ID:PMC2981145
Record Number:CaltechAUTHORS:20190508-134616985
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95353
Deposited By: Tony Diaz
Deposited On:09 May 2019 17:36
Last Modified:03 Oct 2019 21:12

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