title: Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.
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.
authors.affiliation: Cold Spring Harbor Laboratory, Watson School of Biological Sciences and Howard Hughes Medical Institute, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Tam
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Aravin
authors.forename: Paula
authors.initials: P
authors.lastname: Stein
authors.forename: Angelique
authors.initials: A
authors.lastname: Girard
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Murchison
authors.forename: Sihem
authors.initials: S
authors.lastname: Cheloufi
authors.forename: Emily
authors.initials: E
authors.lastname: Hodges
authors.forename: Martin
authors.initials: M
authors.lastname: Anger
authors.forename: Ravi
authors.initials: R
authors.lastname: Sachidanandam
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hannon
mesh_terms: D000818:Animals; D019295:Computational Biology; D004251:DNA Transposable Elements / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D011544:Pseudogenes / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D043244:Ribonuclease III / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D043244:Ribonuclease III