The P Granules of C. elegans: A Genetic Model for the Study of RNA-Protein Condensates - PubMed (original) (raw)

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The P Granules of C. elegans: A Genetic Model for the Study of RNA-Protein Condensates

Geraldine Seydoux. J Mol Biol. 2018.

Abstract

P granules are RNA/protein condensates in the germline of Caenorhabditis elegans. Genetic analyses have begun to identify the proteins that regulate P granule assembly in the cytoplasm of zygotes. Among them, the RGG-domain protein PGL-3, the intrinsically disordered protein MEG-3, and the RNA helicase LAF-1 all bind and phase separate with RNA in vitro. We discuss how RNA-induced phase separation, competition with other RNA-binding proteins, and reversible phosphorylation contribute to the asymmetric localization of P granules in the cytoplasm of newly fertilized embryos. P granules contain RNA silencing complexes that monitor the germline transcriptome and may provide an RNA memory of germline gene expression across generations.

Keywords: C. elegans; Germline condensates; P granules; RNA granules.

Copyright © 2018. Published by Elsevier Ltd.

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Figures

Fig. 1.

Fig. 1.

P granules are present throughout the life cycle of C. elegans. Schematics showing different stages of the C. elegans germline life cycle. In embryos (ovals in figure), P granules segregate asymmetrically with the P lineage that gives rise to the primordial germ cells Z2 and Z3. Z2 and Z3 proliferate during larval stages (not shown) and eventually generate oocytes (square cells, and sperm not shown). P granules (green) are perinuclear during most of germline development. P granules become cytoplasmic in oocytes right before fertilization and return to their perinuclear location in embryos by the 100-cell stage.

Fig. 2.

Fig. 2.

P granule proteins shown to undergo phase separation in vitro. Schematics showing the domain organization of PGL-3, MEG-3 and LAF-1. Intrinsically disordered domains are in green. MEG-3 is rich in serines (14%, yellow lines).

Fig. 3.

Fig. 3.

Genetic hierarchy for P granule asymmetry in zygotes. Schematics summarizing the key results (A) that have led to our understanding of the genetic hierarchy (B) that regulates P granule asymmetry in zygotes. (A) Schematics showing the distribution of MEX-5/6 (pink), MEG-3/4 (orange), and PGL-1/3 (green) in zygotes of the indicated genotypes. In wild type, MEX-5/6 (pink) forms an anterior-rich gradient opposite the posterior-rich MEG-3/4 gradient and the posterior MEG/PGL condensates (P granules). In zygotes lacking PGL-1/3 [_pgl-1/3(0)_], the MEG-3/4 condensates still localize but appear smaller. In zygotes lacking MEG-3/4 [_meg-3/4(0)_], PGL condensates do not localize despite normal formation of the MEX-5/6 gradient. In zygotes lacking MEX-5/6 [_mex-5/6(0)_], MEG/PGL granules form throughout the cytoplasm. In zygotes where MEX-5 is uniformly distributed, MEG/PGL condensates dissolve throughout the cytoplasm (purple). In zygotes where MEX-5 is uniform but lacks its RNA-binding domain (ZF-), MEG/PGL condensates assemble throughout the cytoplasm. (A) Genetic hierarchy: MEX-5/6 gradient localizes MEG-3/4 in an opposite cytoplasmic gradient. MEG-3/4 condensates form scaffolds that stabilize PGL-1/3 condensates.

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