Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.
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.
Tam
Oliver H
OH
Cold Spring Harbor Laboratory, Watson School of Biological Sciences and Howard Hughes Medical Institute, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Aravin
Alexei A
AA
Stein
Paula
P
Girard
Angelique
A
Murchison
Elizabeth P
EP
Cheloufi
Sihem
S
Hodges
Emily
E
Anger
Martin
M
Sachidanandam
Ravi
R
Schultz
Richard M
RM
Hannon
Gregory J
GJ
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
D004251:DNA Transposable Elements; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D043244:Ribonuclease III