Insufficiency of 40S ribosomal proteins, RPS26 and RPS25, negatively affects biosynthesis of polyglycine-containing proteins in fragile-X associated conditions.

ABSTRACT: Expansion of CGG repeats (CGGexp) in the 5' untranslated region (5'UTR) of the FMR1 gene underlies the fragile X premutation-associated conditions including tremor/ataxia syndrome, a late-onset neurodegenerative disease and fragile X-associated primary ovarian insufficiency. One common pathomechanism of these conditions is the repeat-associated non-AUG-initiated (RAN) translation of CGG repeats of mutant FMR1 mRNA, resulting in production of FMRpolyG, a toxic protein containing long polyglycine tract. To identify novel modifiers of RAN translation we used an RNA-tagging system and mass spectrometry-based screening. It revealed proteins enriched on CGGexp-containing FMR1 RNA in cellulo, including a ribosomal protein RPS26, a component of the 40 S subunit. We demonstrate

SUBMITTER: Tutak K 

PROVIDER: S-EPMC12084008 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature