"Protein aggregates" contain RNA and DNA, entrapped by misfolded proteins but largely rescued by slowing translational elongation.

ABSTRACT: All neurodegenerative diseases feature aggregates, which usually contain disease-specific diagnostic proteins; non-protein constituents, however, have rarely been explored. Aggregates from SY5Y-APP_Sw neuroblastoma, a cell model of familial Alzheimer's disease, were crosslinked and sequences of linked peptides identified. We constructed a normalized "contactome" comprising 11 subnetworks, centered on 24 high-connectivity hubs. Remarkably, all 24 are nucleic acid-binding proteins. This led us to isolate and sequence RNA and DNA from Alzheimer's and control aggregates. RNA fragments were mapped to the human genome by RNA-seq and DNA by ChIP-seq. Nearly all aggregate RNA sequences mapped to specific genes, whereas DNA fragments were predominantly intergenic. These nucleic acid mappi

SUBMITTER: Shmookler Reis RJ 

PROVIDER: S-EPMC8135009 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature