title: AGO3 Slicer activity regulates mitochondria-nuage localization of Armitage and piRNA amplification.
abstract: 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.
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
authors: Haidong
authors: H
authors: Huang
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322.
authors: Yujing
authors: Y
authors: Li
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322.
authors: Keith E
authors: KE
authors: Szulwach
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
authors: Guoqiang
authors: G
authors: Zhang
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322 chendh@ioz.ac.cn peng.jin@emory.edu.
authors: Peng
authors: P
authors: Jin
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China chendh@ioz.ac.cn peng.jin@emory.edu.
authors: Dahua
authors: D
authors: Chen
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D008928:Mitochondria / Q000378:metabolism; D030781:Organisms, Genetically Modified / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020365:RNA Helicases / Q000032:analysis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: C518392:AGO3 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; C436124:aub protein, Drosophila; C484034:armi protein, Drosophila; D020365:RNA Helicases