Glutamine missense suppressor transfer RNAs inhibit polyglutamine aggregation.

ABSTRACT: Huntington's disease (HD) is caused by polyglutamine (polyQ) repeat expansions in the huntingtin gene. HD-causative polyQ alleles lead to protein aggregation, which is a prerequisite for disease. Translation fidelity modifies protein aggregation, and several studies suggest that mutating one or two glutamine (Gln) residues in polyQ reduces aggregation. Thus, we hypothesized that missense suppression of Gln codons with other amino acids will reduce polyQ aggregate formation in cells. In neuroblastoma cells, we assessed tRNA variants that misread Gln codons with serine (tRNA^Ser _C/UUG) or alanine (tRNA^Ala _C/UUG). The tRNAs with the CUG anticodon were more effective at suppressing the CAG repeats in polyQ, and serine and alanine mis-incorporation had

SUBMITTER: Tennakoon R 

PROVIDER: S-EPMC11787650 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature