RRC ID 84062
Author Eroglu M, Zocher T, McAuley J, Webster R, Xiao MZX, Yu B, Mok C, Derry WB.
Title Noncanonical inheritance of phenotypic information by protein amyloids.
Journal Nat Cell Biol
Abstract All known heritable phenotypic information in animals is transmitted by direct inheritance of nucleic acids, their covalent modifications or histone modifications that modulate expression of associated genomic regions. Nonetheless, numerous familial traits and disorders cannot be attributed to known heritable molecular factors. Here we identify amyloid-like protein structures that are stably inherited in wild-type animals and influence traits. Their perturbation by genetic, environmental or pharmacological treatments leads to developmental phenotypes that can be epigenetically passed onto progeny. Injection of amyloids isolated from different phenotypic backgrounds into naive animals recapitulates the associated phenotype in offspring. Genetic and proteomic analyses reveal that the 26S proteasome and its conserved regulators maintain heritable amyloids across generations, which enables proper germ cell sex differentiation. We propose that inheritance of a proteinaceous epigenetic memory coordinates developmental timing and patterning with the environment to confer adaptive fitness.
Volume 26(10)
Pages 1712-1724
Published 2024-10-1
DOI 10.1038/s41556-024-01494-9
PII 10.1038/s41556-024-01494-9
PMID 39223373
MeSH Amyloid* / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Epigenesis, Genetic* Female Germ Cells / drug effects Germ Cells / metabolism Inheritance Patterns / genetics Male Phenotype* Proteasome Endopeptidase Complex / genetics Proteasome Endopeptidase Complex / metabolism Proteomics / methods Sex Differentiation / genetics
Resource
C.elegans tm872