Direct and Indirect Protein Interactions Link FUS Aggregation to Histone Post-Translational Modification Dysregulation and Growth Suppression in an ALS/FTD Yeast Model.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are incurable neurodegenerative disorders sharing pathological and genetic features, including mutations in the FUS gene. FUS is an RNA-binding protein that mislocalizes to the cytoplasm and aggregates in ALS/FTD. In a yeast model, FUS proteinopathy is connected to changes in the epigenome, including reductions in the levels of H3S10ph, H3K14ac, and H3K56ac. Exploiting the same model, we reveal novel connections between FUS aggregation and epigenetic dysregulation. We show that the histone-modifying enzymes Ipl1 and Rtt109-responsible for installing H3S10ph and H3K56ac-are excluded from the nucleus in the context of FUS proteinopathy. Furthermore, we found that Ipl1 colocalizes with FUS, but does not bind it direc

SUBMITTER: Bennett SA 

PROVIDER: S-EPMC11766905 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature