RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Dev Cell. 2018 Mar 26;44(6):762-770.e3. doi: 10.1016/j.devcel.2018.01.025. Epub 2018 Feb 15.
In metazoans, Piwi-related Argonaute proteins engage piRNAs (Piwi-interacting small RNAs) to defend the genome against invasive nucleic acids, such as transposable elements. Yet many organisms-including worms and humans-express thousands of piRNAs that do not target transposons, suggesting that piRNA function extends beyond genome defense. Here, we show that the X chromosome-derived piRNA 21ux-1 downregulates XOL-1 (XO Lethal), a master regulator of X chromosome dosage compensation and sex determination in Caenorhabditis elegans. Mutations in 21ux-1 and several Piwi-pathway components sensitize hermaphrodites to dosage compensation and sex determination defects. We show that the piRNA pathway also targets xol-1 in C. briggsae, a nematode species related to C. elegans. Our findings reveal physiologically important piRNA-mRNA interactions, raising the possibility that piRNAs function broadly to ensure robust gene expression and germline development.
在后生动物中，Piwi 相关的 Argonaute 蛋白与 piRNA（Piwi 相互作用的小 RNA）结合，以抵御基因组免受入侵核酸（如转座元件）的侵害。然而，包括蠕虫和人类在内的许多生物表达数千种不针对转座子的 piRNA，表明 piRNA 的功能不仅限于基因组防御。在这里，我们表明，X 染色体衍生的 piRNA 21ux-1 下调 XOL-1（XO 致死），这是秀丽隐杆线虫 X 染色体剂量补偿和性别决定的主要调节剂。21ux-1 和几个 Piwi 通路组件的突变使雌雄同体对剂量补偿和性别决定缺陷敏感。我们表明，piRNA 通路也靶向秀丽隐杆线虫相关的线虫 C. briggsae 中的 xol-1。我们的发现揭示了生理上重要的 piRNA-mRNA 相互作用，这增加了 piRNA 广泛发挥作用以确保稳健的基因表达和生殖细胞发育的可能性。
