Poly(ADP-ribose) drives condensation of FUS via a transient interaction.

ABSTRACT: Poly(ADP-ribose) (PAR) is an RNA-like polymer that regulates an increasing number of biological processes. Dysregulation of PAR is implicated in neurodegenerative diseases characterized by abnormal protein aggregation, including amyotrophic lateral sclerosis (ALS). PAR forms condensates with FUS, an RNA-binding protein linked with ALS, through an unknown mechanism. Here, we demonstrate that a strikingly low concentration of PAR (1 nM) is sufficient to trigger condensation of FUS near its physiological concentration (1 μM), which is three orders of magnitude lower than the concentration at which RNA induces condensation (1 μM). Unlike RNA, which associates with FUS stably, PAR interacts with FUS transiently, triggering FUS to oligomerize into condensates. Moreover, inhibition of a major PAR

SUBMITTER: Rhine K 

PROVIDER: S-EPMC9330637 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature