A nuclear pore-anchored condensate limits transgenerational epigenetic inheritance and regulates the homeostasis of multiphase condensates

ABSTRACT: Many biomolecular condensates such as stress granules, P bodies, nucleoli, and germ granules contain sub-compartments. For instance, the Caenorhabditis elegans germ granule, which localizes near the outer nuclear membrane of germ cell nuclei, is composed of at least four ordered compartments, each housing distinct sets of proteins and RNAs. How these compartments might form, and why these compartments are ordered in space, remain poorly understood. Here we show that the conserved RNA helicase DDX-19 defines another compartment of the larger Caenorhabditis elegans germ granule, which we name the D compartment. We find that the D compartment exhibits properties of a liquid condensate and that it localizes between the outer nuclear pore filament and other compartments of the germ granule. Two nuclear pore proteins NPP-14 and GLE-1, whose homologs are known to interact with DDX-19 homologs in other eukaryotes, are required for D compartment formation, suggesting that the D compartment localizes adjacent to the outer nuclear membrane via interactions with the nuclear pore. The loss of DDX-19, NPP-14, or GLE-1 leads to; 1) aberrant morphology, assembly, and ordering of the other four germ granule compartments; 2) a loss of germline immortality; and 3) dysregulation of RNA-based transgenerational epigenetic inheritance programs. Hence, we propose that one function of DDX-19 and the D compartment is to help anchor the larger germ granule to nuclear pores, which enables germ granule compartmentalization and empowers transgenerational RNA surveillance.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Caenorhabditis Elegans

TISSUE(S): Whole Body

SUBMITTER: Boyuan Deng  

LAB HEAD: Gang Wan

PROVIDER: PXD056752 | Pride | 2025-02-09

REPOSITORIES: pride