AGO3 Slicer activity regulates mitochondria-nuage localization of Armitage and piRNA amplification.
AGO3 Slicer activity regulates mitochondria-nuage localization of Armitage and piRNA amplification.
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AGO3 Slicer 活性调节 Armitage 和 piRNA 扩增的线粒体 -nuage 定位
DOI：
10.1083/jcb.201401002
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发表时间：
2014-07-21
期刊：
影响因子：
--
通讯作者：
Chen D
中科院分区：
文献类型：
--
作者：
Huang H;Li Y;Szulwach KE;Zhang G;Jin P;Chen D
核酸内切酶AGO_3和线粒体相关蛋白Zucchini共同控制Armitage在线粒体和生殖系颗粒之间的动态亚细胞定位，以调节二级piRNA扩增。在果蝇中，由PIWI蛋白Aubergine(Aub)和ArgAerte3(AG03)的内切酶(或Slicer)活性催化的PIWI相互作用RNA(PiRNA)引导的RNA切割的倒数“乒乓”循环被认为是为了扩大次级piRNA种群。然而，Ag03/Aub Slicer活性在piRNA扩增中的作用仍有待探讨。我们证明了AGO_3的切片子活性对于piRNA扩增是必不可少的，并且AGO_3以不依赖于切片子的方式抑制同型AuB：AUB乒乓球过程。我们还发现，AG03 Slicer突变体的表达导致了Armitage的异位积累，Armitage是初级piRNA途径的关键成分，在果蝇黑腹果蝇胚系颗粒中被称为nuage。AgO_3在线粒体部分也与Armitage共存并相互作用。此外，AG03与线粒体相关蛋白Zucchini共同作用，以Slicer依赖的方式控制线粒体和Nuage之间Armitage的动态亚细胞定位。总体而言，我们的发现揭示了一种新的机制，即将线粒体与Nuage偶联来调节二级piRNA扩增。
The endonuclease AGO3 and mitochondria-associated protein Zucchini together control the dynamic subcellular localization of Armitage between mitochondria and germline granules to regulate secondary piRNA amplification. In Drosophila melanogaster the reciprocal “Ping-Pong” cycle of PIWI-interacting RNA (piRNA)–directed RNA cleavage catalyzed by the endonuclease (or “Slicer”) activities of the PIWI proteins Aubergine (Aub) and Argonaute3 (AGO3) has been proposed to expand the secondary piRNA population. However, the role of AGO3/Aub Slicer activity in piRNA amplification remains to be explored. We show that AGO3 Slicer activity is essential for piRNA amplification and that AGO3 inhibits the homotypic Aub:Aub Ping-Pong process in a Slicer-independent manner. We also find that expression of an AGO3 Slicer mutant causes ectopic accumulation of Armitage, a key component in the primary piRNA pathway, in the Drosophila melanogaster germline granules known as nuage. AGO3 also coexists and interacts with Armitage in the mitochondrial fraction. Furthermore, AGO3 acts in conjunction with the mitochondria-associated protein Zucchini to control the dynamic subcellular localization of Armitage between mitochondria and nuage in a Slicer-dependent fashion. Collectively, our findings uncover a new mechanism that couples mitochondria with nuage to regulate secondary piRNA amplification.
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影响因子：
16
作者：
Handler, Dominik;Meixner, Katharina;Pizka, Manfred;Lauss, Kathrin;Schmied, Christopher;Gruber, Franz Sebastian;Brennecke, Julius
通讯作者：
Brennecke, Julius
影响因子：
64.8
作者：
Nishimasu, Hiroshi;Ishizu, Hirotsugu;Nureki, Osamu
通讯作者：
Nureki, Osamu
影响因子：
10.5
作者：
Okamura, K;Ishizuka, A;Siomi, MC
通讯作者：
Siomi, MC
影响因子：
64.5
作者：
Brennecke, Julius;Aravin, Alexei A.;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
影响因子：
56.9
作者：
Gunawardane, Lalith S.;Saito, Kuniaki;Siomi, Mikiko C.
通讯作者：
Siomi, Mikiko C.