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

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

doi:10.7554/elife.04591

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.

Highlights

RNA granules are ubiquitous cytoplasmic organelles that contain RNA and RNA-binding proteins (Kedersha et al, 2013; Buchan, 2014)
Live imaging studies in Caenorhabditis elegans zygotes have suggested that RNA granules behave like liquid droplets that undergo phase transitions (Brangwynne et al, 2009)
To determine the earliest time point at which P granules become dynamic during the oocyte-tozygote transition, we monitored P granules in the oviduct and uteri of live hermaphrodites from ovulation through the first embryonic divisions

Summary

Introduction

RNA granules are ubiquitous cytoplasmic organelles that contain RNA and RNA-binding proteins (Kedersha et al, 2013; Buchan, 2014). Several types of RNA granules have been described, including germ granules in germ cells, neuronal granules in neurons, and stress granules and P bodies in somatic cells. Their functions include mRNA transport and storage and the regulation of mRNA degradation and translation. Live imaging studies in Caenorhabditis elegans zygotes have suggested that RNA granules behave like liquid droplets that undergo phase transitions (Brangwynne et al, 2009). The proteins that drive the phase transitions in vivo, are not known

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Results

Conclusion