Molecular insights into the interaction of CAG trinucleotide RNA repeats with nucleolin and its implication in polyglutamine diseases.

ABSTRACT: Polyglutamine (polyQ) diseases are a type of inherited neurodegenerative disorders caused by cytosine-adenine-guanine (CAG) trinucleotide expansion within the coding region of the disease-associated genes. We previously demonstrated that a pathogenic interaction between expanded CAG RNA and the nucleolin (NCL) protein triggers the nucleolar stress and neuronal cell death in polyQ diseases. However, mechanisms behind the molecular interaction remain unknown. Here, we report a 1.45 Å crystal structure of the r(CAG)5 oligo that comprises a full A'-form helical turn with widened grooves. Based on this structure, we simulated a model of r(CAG)5 RNA complexed with the RNA recognition motif 2 (RRM2) of NCL and identified NCL residues that are critical for its binding to CAG RNA. Combined with in

SUBMITTER: An Y 

PROVIDER: S-EPMC9303306 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature