title: Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans.
abstract: RNA granules have been likened to liquid droplets whose dynamics depend on the controlled dissolution and condensation of internal components. The molecules and reactions that drive these dynamics in vivo are not well understood. In this study, we present evidence that a group of intrinsically disordered, serine-rich proteins regulate the dynamics of P granules in C. elegans embryos. The MEG (maternal-effect germline defective) proteins are germ plasm components that are required redundantly for fertility. We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2A(PPTR-½). Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly. Using lattice light sheet microscopy on live embryos, we show that GFP-tagged MEG-3 localizes to a dynamic domain that surrounds and penetrates each granule. We conclude that, despite their liquid-like behavior, P granules are non-homogeneous structures whose assembly in embryos is regulated by phosphorylation.
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Jarrett
authors.initials: J
authors.lastname: Smith
authors.affiliation: Research Center for Applied Sciences, Academica Sinica, Taipei, Taiwan.
authors.forename: Bi-Chang
authors.initials: BC
authors.lastname: Chen
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Helen
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Dominique
authors.initials: D
authors.lastname: Rasoloson
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Paix
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Bramwell G
authors.initials: BG
authors.lastname: Lambrus
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Deepika
authors.initials: D
authors.lastname: Calidas
authors.affiliation: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
authors.forename: Eric
authors.initials: E
authors.lastname: Betzig
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Seydoux
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000737:chemistry* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D017510:Protein Folding; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D018510:RNA, Helminth / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C561413:MEG-1 protein, C elegans; D018510:RNA, Helminth; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D012694:Serine; C478059:MBK-2 protein, C elegans; D011505:Protein-Tyrosine Kinases; D054648:Protein Phosphatase 2
keywords: C. elegans; RNA granules; cell biology; developmental biology; germ plasm; intrinsically disordered proteins; stem cells