title: Modifiers of solid RNP granules control normal RNP dynamics and mRNA activity in early development.
abstract: Ribonucleoproteins (RNPs) often coassemble into supramolecular bodies with regulated dynamics. The factors controlling RNP bodies and connections to RNA regulation are unclear. During Caenorhabditis elegans oogenesis, cytoplasmic RNPs can transition among diffuse, liquid, and solid states linked to mRNA regulation. Loss of CGH-1/Ddx6 RNA helicase generates solid granules that are sensitive to mRNA regulators. Here, we identified 66 modifiers of RNP solids induced by cgh-1 mutation. A majority of genes promote or suppress normal RNP body assembly, dynamics, or metabolism. Surprisingly, polyadenylation factors promote RNP coassembly in vivo, suggesting new functions of poly(A) tail regulation in RNP dynamics. Many genes carry polyglutatmine (polyQ) motifs or modulate polyQ aggregation, indicating possible connections with neurodegenerative disorders induced by CAG/polyQ expansion. Several RNP body regulators repress translation of mRNA subsets, suggesting that mRNAs are repressed by multiple mechanisms. Collectively, these findings suggest new pathways of RNP modification that control large-scale coassembly and mRNA activity during development.
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 Pierre-and-Marie-Curie University, University Paris 06, 75005 Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Hubstenberger
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Cameron
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 Graduate Program in Molecular Biology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Noble
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
authors.forename: Sean
authors.initials: S
authors.lastname: Keenan
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 tom.evans@ucdenver.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Evans
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D009866:Oogenesis / Q000235:genetics; D012316:RNA Nucleotidyltransferases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D012261:Ribonucleoproteins / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D012316:RNA Nucleotidyltransferases; C490618:cgh-1 protein, C elegans