RNA-binding proteins with basic-acidic dipeptide (BAD) domains self-assemble and aggregate in Alzheimer's disease.

ABSTRACT: The U1 small nuclear ribonucleoprotein 70 kDa (U1-70K) and other RNA-binding proteins (RBPs) are mislocalized to cytoplasmic neurofibrillary Tau aggregates in Alzheimer's disease (AD), yet the co-aggregation mechanisms are incompletely understood. U1-70K harbors two disordered low-complexity domains (LC1 and LC2) that are necessary for aggregation in AD brain extracts. The LC1 domain contains highly repetitive basic (Arg/Lys) and acidic (Asp/Glu) residues, referred to as a basic-acidic dipeptide (BAD) domain. We report here that this domain shares many of the properties of the Gln/Asn-rich LC domains in RBPs that also aggregate in neurodegenerative disease. These properties included self-assembly into oligomers and localization to nuclear granules. Co-immunoprecipitations of recombinant U1

SUBMITTER: Bishof I 

PROVIDER: S-EPMC6052236 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature