Ribosomal aminoacyl-tRNA binding site (A-site) (A-site)

The ribosomal aminoacyl-tRNA binding site (A-site) is the critical decoding center within the ribosome where mRNA codons are matched with their corresponding aminoacyl-tRNAs during protein synthesis [PMID: 11514515]. In patients with Duchenne muscular dystrophy (DMD) caused by nonsense mutations, a premature termination codon (PTC) is present in the dystrophin mRNA, which leads to the premature cessation of translation and the production of truncated, non-functional dystrophin protein [PMID: 26866211]. Therapeutic agents such as ataluren and certain aminoglycosides target the ribosomal A-site to induce "read-through" of these PTCs [PMID: 24835150]. By binding to the A-site, these molecules reduce the fidelity of the decoding process, allowing a near-cognate aminoacyl-tRNA to be incorporated instead of a release factor [PMID: 11514515]. This allows the ribosome to continue translation to the natural stop codon, resulting in the synthesis of a full-length, functional dystrophin protein [PMID: 24835150]. This approach is specifically designed for the subset of DMD patients whose disease results from nonsense mutations, representing a personalized medicine strategy for restoring essential protein function [PMID: 26866211].

Other names

Ribosomal aminoacyl-tRNA binding siteDecoding centerPTC read-through siteRibosomal A-site decoding of premature termination codons in dystrophin mRNA

Nonsense mutation read-through via suppression of premature termination codons