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HERD-1 mediates multiphase condensate immiscibility to regulate small RNA-driven transgenerational epigenetic inheritance.
Zhao, Changfeng; Cai, Shiyu; Shi, Ruona; Li, Xinru; Deng, Boyuan; Li, Ruofei; Yang, Shuhan; Huang, Jing; Liang, Yonglin; Lu, Pu; Yuan, Zhongping; Jia, Haoxiang; Jiang, Zongjin; Zhang, Xiaofei; Kennedy, Scott; Wan, Gang.
Afiliação
  • Zhao C; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Cai S; Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Shi R; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Li X; Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Deng B; CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Li R; Center for Cell Lineage and Atlas, Bioland Laboratory, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China.
  • Yang S; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Huang J; Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Liang Y; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Lu P; Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Yuan Z; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Jia H; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Jiang Z; Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Zhang X; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Kennedy S; Innovation Center for Evolutionary Synthetic Biology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Wan G; Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
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

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