Stochastic Seeding Coupled with mRNA Self-Recruitment Generates Heterogeneous Drosophila Germ Granules. Author Matthew Niepielko, Whitby Eagle, Elizabeth Gavis Publication Year 2018 Type Journal Article Abstract The formation of ribonucleoprotein assemblies called germ granules is a conserved feature of germline development. In Drosophila, germ granules form at the posterior of the oocyte in a specialized cytoplasm called the germ plasm, which specifies germline fate during embryogenesis. mRNAs, including nanos (nos) and polar granule component (pgc), that function in germline development are localized to the germ plasm through their incorporation into germ granules, which deliver them to the primordial germ cells. Germ granules are nucleated by Oskar (Osk) protein and contain varying combinations and quantities of their constituent mRNAs, which are organized as spatially distinct, multi-copy homotypic clusters. The process that gives rise to such heterogeneous yet organized granules remains unknown. Here, we show that individual nos and pgc transcripts can populate the same nascent granule, and these first transcripts then act as seeds, recruiting additional like transcripts to form homotypic clusters. Within a granule, homotypic clusters grow independently of each other but depend on the simultaneous acquisition of additional Osk. Although granules can contain multiple clusters of a particular mRNA, granule mRNA content is dominated by cluster size. These results suggest that the accumulation of mRNAs in the germ plasm is controlled by the mRNAs themselves through their ability to form homotypic clusters; thus, RNA self-association drives germ granule mRNA localization. We propose that a stochastic seeding and self-recruitment mechanism enables granules to simultaneously incorporate many different mRNAs while ensuring that each becomes enriched to a functional threshold. Keywords Animals, Drosophila Proteins, RNA-Binding Proteins, RNA, Messenger, Drosophila melanogaster, Embryonic Development, Embryo, Nonmammalian, Cytoplasmic Granules, Positive Transcriptional Elongation Factor B, Germ Cells Journal Curr Biol Volume 28 Issue 12 Pages 1872-1881.e3 Date Published 2018 Jun 18 ISSN Number 1879-0445 DOI 10.1016/j.cub.2018.04.037 Alternate Journal Curr Biol PMCID PMC6008217 PMID 29861136 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML