title: Arginine methylation of Aubergine mediates Tudor binding and germ plasm localization.
abstract: Piwi proteins such as Drosophila Aubergine (Aub) and mouse Miwi are essential for germline development and for primordial germ cell (PGC) specification. They bind piRNAs and contain symmetrically dimethylated arginines (sDMAs), catalyzed by dPRMT5. PGC specification in Drosophila requires maternal inheritance of cytoplasmic factors, including Aub, dPRMT5, and Tudor (Tud), that are concentrated in the germ plasm at the posterior end of the oocyte. Here we show that Miwi binds to Tdrd6 and Aub binds to Tudor, in an sDMA-dependent manner, demonstrating that binding of sDMA-modified Piwi proteins with Tudor-domain proteins is an evolutionarily conserved interaction in germ cells. We report that in Drosophila tud(1) mutants, the piRNA pathway is intact and most transposons are not de-repressed. However, the localization of Aub in the germ plasm is severely reduced. These findings indicate that germ plasm assembly requires sDMA modification of Aub by dPRMT5, which, in turn, is required for binding to Tudor. Our study also suggests that the function of the piRNA pathway in PGC specification may be independent of its role in transposon control.
authors.affiliation: Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine,Philadelphia, Pennsylvania 19104, USA.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kirino
authors.forename: Anastassios
authors.initials: A
authors.lastname: Vourekas
authors.forename: Nabil
authors.initials: N
authors.lastname: Sayed
authors.forename: Flavia
authors.initials: F
authors.lastname: de Lima Alves
authors.forename: Travis
authors.initials: T
authors.lastname: Thomson
authors.forename: Paul
authors.initials: P
authors.lastname: Lasko
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Jongens
authors.forename: Zissimos
authors.initials: Z
authors.lastname: Mourelatos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D005260:Female; D005854:Germ Cells / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000378:metabolism*; D011485:Protein Binding; D011496:Protein Methyltransferases / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D029721:Drosophila Proteins; D026901:Membrane Transport Proteins; D010448:Peptide Initiation Factors; C436124:aub protein, Drosophila; C071597:tud protein, Drosophila; D001120:Arginine; D011496:Protein Methyltransferases; D011484:Protein-Arginine N-Methyltransferases; C512734:csul protein, Drosophila