Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans

Jennifer T. Wang; Jarrett Smith; Bi Chang Chen; Helen Schmidt; Dominique Rasoloson; Alexandre Paix; Bramwell G. Lambrus; Deepika Calidas; Eric Betzig; Geraldine Seydoux

doi:10.7554/eLife.04591

Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans

Jennifer T. Wang, Jarrett Smith, Bi Chang Chen, Helen Schmidt, Dominique Rasoloson, Alexandre Paix, Bramwell G. Lambrus, Deepika Calidas, Eric Betzig, Geraldine Seydoux

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201 Scopus citations

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.

Original language	English (US)
Article number	e04591
Journal	eLife
Volume	3
DOIs	https://doi.org/10.7554/eLife.04591
State	Published - 2014

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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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 PP2APPTR−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.",

author = "Wang, {Jennifer T.} and Jarrett Smith and Chen, {Bi Chang} and Helen Schmidt and Dominique Rasoloson and Alexandre Paix and Lambrus, {Bramwell G.} and Deepika Calidas and Eric Betzig and Geraldine Seydoux",

note = "Funding Information: We thank Valerie Reinke, Sam Kapelle, Karen Bennett, the National Bioresource Center (Japan), and the CGC (USA) for strains and reagents, the Janelia Farm Visitors Program for hosting Jenn Wang, and Cliff Brangwynne and the Seydoux lab for discussions. Research in the Seydoux lab is supported by R01HD37047 from the National Institutes of Health. G Seydoux is an Investigator of the Howard Hughes Medical Institute. Research in the Betzig lab is wholly supported by the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} Wang et al.",

year = "2014",

doi = "10.7554/eLife.04591",

language = "English (US)",

volume = "3",

journal = "eLife",

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AU - Wang, Jennifer T.

AU - Smith, Jarrett

AU - Chen, Bi Chang

AU - Schmidt, Helen

AU - Rasoloson, Dominique

AU - Paix, Alexandre

AU - Lambrus, Bramwell G.

AU - Calidas, Deepika

AU - Betzig, Eric

AU - Seydoux, Geraldine

N1 - Funding Information: We thank Valerie Reinke, Sam Kapelle, Karen Bennett, the National Bioresource Center (Japan), and the CGC (USA) for strains and reagents, the Janelia Farm Visitors Program for hosting Jenn Wang, and Cliff Brangwynne and the Seydoux lab for discussions. Research in the Seydoux lab is supported by R01HD37047 from the National Institutes of Health. G Seydoux is an Investigator of the Howard Hughes Medical Institute. Research in the Betzig lab is wholly supported by the Howard Hughes Medical Institute. Publisher Copyright: © Wang et al.

PY - 2014

Y1 - 2014

N2 - 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 PP2APPTR−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.

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Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically disordered proteins in C. elegans

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