HERD-1 mediates multiphase condensate immiscibility to regulate small RNA-driven transgenerational epigenetic inheritance.
Nat Cell Biol
; 2024 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-39354132
ABSTRACT
Biomolecular condensates, such as the nucleolus, stress granules/processing bodies and germ granules, are multiphase assemblages whose formation mechanisms and significance remain poorly understood. Here we identify protein constituents of the spatiotemporally ordered P, Z and M multiphase condensates in Caenorhabditis elegans germ granules using optimized TurboID-mediated proximity biotin labelling. These include 462, 41 and 86 proteins localizing to P, Z and M condensates, respectively, of which 522 were previously unknown protein constituents. Each condensate's proteins are enriched for distinct classes of structured and intrinsically disordered domains, suggesting divergent functions and assembly mechanisms. Through a functional screen, we identify a germ granule protein, HERD-1, which prevents the mixing of P, Z and M condensates. Mixing in herd-1 mutants correlates with disorganization of germline small RNA pathways and prolonged epigenetic inheritance of RNA interference-induced gene silencing. Forced mixing of these condensate components using a nanobody with specific binding activity against green fluorescent protein also extends epigenetic inheritance. We propose that active maintenance of germ granule immiscibility helps to organize and regulate small RNA-driven transgenerational epigenetic inheritance in C. elegans.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Reino Unido