RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.
RNA Therapeutics Institute and Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA; Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Mol Cell. 2019 Jun 6;74(5):982-995.e6. doi: 10.1016/j.molcel.2019.04.006. Epub 2019 May 7.
PIWI-interacting RNAs (piRNAs) silence transposons in Drosophila ovaries, ensuring female fertility. Two coupled pathways generate germline piRNAs: the ping-pong cycle, in which the PIWI proteins Aubergine and Ago3 increase the abundance of pre-existing piRNAs, and the phased piRNA pathway, which generates strings of tail-to-head piRNAs, one after another. Proteins acting in the ping-pong cycle localize to nuage, whereas phased piRNA production requires Zucchini, an endonuclease on the mitochondrial surface. Here, we report that Armitage (Armi), an RNA-binding ATPase localized to both nuage and mitochondria, links the ping-pong cycle to the phased piRNA pathway. Mutations that block phased piRNA production deplete Armi from nuage. Armi ATPase mutants cannot support phased piRNA production and inappropriately bind mRNA instead of piRNA precursors. We propose that Armi shuttles between nuage and mitochondria, feeding precursor piRNAs generated by Ago3 cleavage into the Zucchini-dependent production of Aubergine- and Piwi-bound piRNAs on the mitochondrial surface.
PIWI 相互作用 RNA(piRNAs)在果蝇卵巢中沉默转座子,确保雌性的生育能力。两种偶联途径产生生殖系 piRNAs:乒乓循环,其中 PIWI 蛋白 Aubergine 和 Ago3 增加预先存在的 piRNAs 的丰度,以及相分离 piRNA 途径,其连续生成头对头的 piRNA 串。在乒乓循环中起作用的蛋白质定位于 nuage,而相分离 piRNA 的产生需要 Zucchini,一种位于线粒体表面的内切核酸酶。在这里,我们报告说,定位于 nuage 和线粒体的 RNA 结合 ATP 酶 Armitage(Armi)将乒乓循环与相分离 piRNA 途径联系起来。阻断相分离 piRNA 产生的突变会使 Armi 从 nuage 中耗尽。Armi ATP 酶突变体不能支持相分离 piRNA 的产生,并且错误地结合 mRNA 而不是 piRNA 前体。我们提出,Armi 在 nuage 和线粒体之间穿梭,将由 Ago3 切割产生的前体 piRNAs 供给 Zucchini,从而在线粒体表面产生 Aubergine 和 Piwi 结合的 piRNAs。