Department of Developmental Biology, Sloan-Kettering Institute, New York, NY 10065, USA.
Curr Biol. 2009 Dec 29;19(24):2066-76. doi: 10.1016/j.cub.2009.11.064.
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.
Piwi 相互作用 RNA（piRNA）是大约 24-30 个核苷酸的调节 RNA，在动物性腺和早期胚胎中丰富存在。研究最深入的 piRNA 介导了一种保守的途径，限制转座元件，并且这些途径经常涉及“乒乓”扩增环。某些哺乳动物睾丸阶段也积累了大量未知功能的 piRNA，这些 piRNA 来源于非编码 RNA，这些 RNA 缺乏转座元件含量，并且不参与乒乓反应。
我们报告称，大量信使 RNA（mRNA）的 3'非翻译区（3'UTR）在果蝇卵巢、小鼠睾丸和爪蟾卵中被加工成 piRNA。对不同突变体和 Piwi 类免疫沉淀的分析表明，它们的生物发生依赖于初级 piRNA 成分，但不依赖于大多数乒乓成分。有几个观察结果表明，mRNA 被主动选择用于产生 piRNA，以实现调节目的。首先，基因 piRNA 的积累与它们宿主转录物的水平不成比例，并且许多高表达的转录物缺乏 piRNA。其次，果蝇和小鼠中产生 piRNA 的 mRNA 富含与简单丰富转录物不同的特定基因本体类别。第三，交通拥堵的蛋白质输出，其 3'UTR 产生大量的 piRNA，在 piwi 突变体卵泡克隆中增加。
我们揭示了一种保守的初级 piRNA 途径，该途径选择和代谢广泛的细胞转录物的 3'UTR，可能用于调节目的。这些发现极大地增加了后生动物 Argonaute 介导的小 RNA 系统的广度。
