Sequence-Independent Self-Assembly of Germ Granule mRNAs into Homotypic Clusters. Author Tatjana Trcek, Tyler Douglas, Markus Grosch, Yandong Yin, Whitby Eagle, Elizabeth Gavis, Hari Shroff, Eli Rothenberg, Ruth Lehmann Publication Year 2020 Type Journal Article Abstract mRNAs enriched in membraneless condensates provide functional compartmentalization within cells. The mechanisms that recruit transcripts to condensates are under intense study; however, how mRNAs organize once they reach a granule remains poorly understood. Here, we report on a self-sorting mechanism by which multiple mRNAs derived from the same gene assemble into discrete homotypic clusters. We demonstrate that in vivo mRNA localization to granules and self-assembly within granules are governed by different mRNA features: localization is encoded by specific RNA regions, whereas self-assembly involves the entire mRNA, does not involve sequence-specific, ordered intermolecular RNA:RNA interactions, and is thus RNA sequence independent. We propose that the ability of mRNAs to self-sort into homotypic assemblies is an inherent property of an messenger ribonucleoprotein (mRNP) that is augmented under conditions that increase RNA concentration, such as upon enrichment in RNA-protein granules, a process that appears conserved in diverse cellular contexts and organisms. Keywords Animals, Drosophila Proteins, Nuclear Proteins, RNA, Messenger, RNA, Drosophila melanogaster, Ribonucleoproteins, RNA Transport, Cytoplasmic Granules, Organelles Journal Mol Cell Volume 78 Issue 5 Pages 941-950.e12 Date Published 2020 Jun 04 ISSN Number 1097-4164 DOI 10.1016/j.molcel.2020.05.008 Alternate Journal Mol Cell PMCID PMC7325742 PMID 32464092 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML