title: Aub and Ago3 Are Recruited to Nuage through Two Mechanisms to Form a Ping-Pong Complex Assembled by Krimper.
abstract: In Drosophila, two Piwi proteins, Aubergine (Aub) and Argonaute-3 (Ago3), localize to perinuclear "nuage" granules and use guide piRNAs to target and destroy transposable element transcripts. We find that Aub and Ago3 are recruited to nuage by two different mechanisms. Aub requires a piRNA guide for nuage recruitment, indicating that its localization depends on recognition of RNA targets. Ago3 is recruited to nuage independently of a piRNA cargo and relies on interaction with Krimper, a stable component of nuage that is able to aggregate in the absence of other nuage proteins. We show that Krimper interacts directly with Aub and Ago3 to coordinate the assembly of the ping-pong piRNA processing (4P) complex. Symmetrical dimethylated arginines are required for Aub to interact with Krimper, but they are dispensable for Ago3 to bind Krimper. Our study reveals a multi-step process responsible for the assembly and function of nuage complexes in piRNA-guided transposon repression.
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Alexandre
authors: A
authors: Webster
authors: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021 USA.
authors: Sisi
authors: S
authors: Li
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Junho K
authors: JK
authors: Hur
authors: Cell Biology & Biophysics Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
authors: Malte
authors: M
authors: Wachsmuth
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Justin S
authors: JS
authors: Bois
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Edward M
authors: EM
authors: Perkins
authors: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021 USA.
authors: Dinshaw J
authors: DJ
authors: Patel
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: aaa@caltech.edu.
authors: Alexei A
authors: AA
authors: Aravin
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D010448:Peptide Initiation Factors / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: C518392:AGO3 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; C000602673:Krimp protein, Drosophila; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; C436124:aub protein, Drosophila