title: Sequence-dependent but not sequence-specific piRNA adhesion traps mRNAs to the germ plasm.
abstract: The conserved Piwi family of proteins and piwi-interacting RNAs (piRNAs) have a central role in genomic stability, which is inextricably linked to germ-cell formation, by forming Piwi ribonucleoproteins (piRNPs) that silence transposable elements. In Drosophila melanogaster and other animals, primordial germ-cell specification in the developing embryo is driven by maternal messenger RNAs and proteins that assemble into specialized messenger ribonucleoproteins (mRNPs) localized in the germ (pole) plasm at the posterior of the oocyte. Maternal piRNPs, especially those loaded on the Piwi protein Aubergine (Aub), are transmitted to the germ plasm to initiate transposon silencing in the offspring germ line. The transport of mRNAs to the oocyte by midoogenesis is an active, microtubule-dependent process; mRNAs necessary for primordial germ-cell formation are enriched in the germ plasm at late oogenesis via a diffusion and entrapment mechanism, the molecular identity of which remains unknown. Aub is a central component of germ granule RNPs, which house mRNAs in the germ plasm, and interactions between Aub and Tudor are essential for the formation of germ granules. Here we show that Aub-loaded piRNAs use partial base-pairing characteristics of Argonaute RNPs to bind mRNAs randomly in Drosophila, acting as an adhesive trap that captures mRNAs in the germ plasm, in a Tudor-dependent manner. Notably, germ plasm mRNAs in drosophilids are generally longer and more abundant than other mRNAs, suggesting that they provide more target sites for piRNAs to promote their preferential tethering in germ granules. Thus, complexes containing Tudor, Aub piRNPs and mRNAs couple piRNA inheritance with germline specification. Our findings reveal an unexpected function for piRNP complexes in mRNA trapping that may be generally relevant to the function of animal germ granules.
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine; PENN Genome Frontiers Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Anastassios
authors.initials: A
authors.lastname: Vourekas
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine; PENN Genome Frontiers Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexiou
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine; PENN Genome Frontiers Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Vrettos
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine; PENN Genome Frontiers Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Manolis
authors.initials: M
authors.lastname: Maragkakis
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine; PENN Genome Frontiers Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Zissimos
authors.initials: Z
authors.lastname: Mourelatos
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D020029:Base Pairing; D001665:Binding Sites; D003593:Cytoplasm / Q000235:genetics* / Q000378:metabolism*; D004251:DNA Transposable Elements / Q000235:genetics; D004058:Diffusion; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism; D009866:Oogenesis; D010448:Peptide Initiation Factors / Q000378:metabolism; D034622:RNA Interference; D034443:RNA Transport; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: D060565:Argonaute Proteins; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D026901:Membrane Transport Proteins; D010448:Peptide Initiation Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; C436124:aub protein, Drosophila; C071597:tud protein, Drosophila