A broadly conserved pathway generates 3''UTR-directed primary piRNAs.
Piwi-interacting RNAs (piRNAs) are approximately 24-30 nucleotide regulatory RNAs that are abundant in animal gonads and early embryos. The best-characterized piRNAs mediate a conserved pathway that restricts transposable elements, and these frequently engage a "ping-pong" amplification loop. Certain stages of mammalian testis also accumulate abundant piRNAs of unknown function, which derive from noncoding RNAs that are depleted in transposable element content and do not engage in ping-pong.We report that the 3'' untranslated regions (3''UTRs) of an extensive set of messenger RNAs (mRNAs) are processed into piRNAs in Drosophila ovaries, murine testes, and Xenopus eggs. Analysis of different mutants and Piwi-class immunoprecipitates indicates that their biogenesis depends on primary piRNA components, but not most ping-pong components. Several observations suggest that mRNAs are actively selected for piRNA production for regulatory purposes. First, genic piRNAs do not accumulate in proportion to the level of their host transcripts, and many highly expressed transcripts lack piRNAs. Second, piRNA-producing mRNAs in Drosophila and mouse are enriched for specific gene ontology categories distinct from those of simply abundant transcripts. Third, the protein output of traffic jam, whose 3''UTR generates abundant piRNAs, is increased in piwi mutant follicle clones.We reveal a conserved primary piRNA pathway that selects and metabolizes the 3''UTRs of a broad set of cellular transcripts, probably for regulatory purposes. These findings strongly increase the breadth of Argonaute-mediated small RNA systems in metazoans.
PubMed ID: 20022248
PMC ID: PMC2812478
Article link: Curr Biol.
Grant support: GM086434 NIGMS NIH HHS , GM48405 NIGMS NIH HHS , HD057298 NICHD NIH HHS , R01-GM083300 NIGMS NIH HHS , U01-HG004261 NHGRI NIH HHS , R01 GM083300-03 NIGMS NIH HHS , U01 HG004261-03 NHGRI NIH HHS , K99 HD057298 NICHD NIH HHS , R00 HD057298 NICHD NIH HHS
Genes referenced: f11r piwil1