title: PAPI, a novel TUDOR-domain protein, complexes with AGO3, ME31B and TRAL in the nuage to silence transposition.
abstract: The nuage is a germline-specific perinuclear structure that remains functionally elusive. Recently, the nuage in Drosophila was shown to contain two of the three PIWI proteins - Aubergine and Argonaute 3 (AGO3) - that are essential for germline development. The PIWI proteins bind to PIWI-interacting RNAs (piRNAs) and function in epigenetic regulation and transposon control. Here, we report a novel nuage component, PAPI (Partner of PIWIs), that contains a TUDOR domain and interacts with all three PIWI proteins via symmetrically dimethylated arginine residues in their N-terminal domain. In adult ovaries, PAPI is mainly cytoplasmic and enriched in the nuage, where it partially colocalizes with AGO3. The localization of PAPI to the nuage does not require the arginine methyltransferase dPRMT5 or AGO3. However, AGO3 is largely delocalized from the nuage and becomes destabilized in the absence of PAPI or dPRMT5, indicating that PAPI recruits PIWI proteins to the nuage to assemble piRNA pathway components. As expected, papi deficiency leads to transposon activation, phenocopying piRNA mutants. This further suggests that PAPI is involved in the piRNA pathway for transposon silencing. Moreover, AGO3 and PAPI associate with the P body component TRAL/ME31B complex in the nuage and transposon activation is observed in tral mutant ovaries. This suggests a physical and functional interaction in the nuage between the piRNA pathway components and the mRNA-degrading P-body components in transposon silencing. Overall, our study reveals a function of the nuage in safeguarding the germline genome against deleterious retrotransposition via the piRNA pathway.
authors: Yale Stem Cell Center and Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06509, USA.
authors: Li
authors: L
authors: Liu
authors: Hongying
authors: H
authors: Qi
authors: Jianquan
authors: J
authors: Wang
authors: Haifan
authors: H
authors: Lin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D060565:Argonaute Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004251:DNA Transposable Elements / Q000235:genetics* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing / Q000502:physiology; D005854:Germ Cells / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008954:Models, Biological; D016254:Mutagenesis, Insertional / Q000235:genetics; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: C518392:AGO3 protein, Drosophila; D060565:Argonaute Proteins; D002352:Carrier Proteins; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; C558830:PAPI protein, drosophila; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D034743:RNA-Induced Silencing Complex; D012261:Ribonucleoproteins; C516259:TRAL protein, Drosophila; C116498:piwi protein, Drosophila; C532748:Me31B protein, Drosophila; D053487:DEAD-box RNA Helicases