Premature termination codon (PTC) in mRNA (PTC)

The premature termination codon (PTC) in mRNA, specifically the UGA codon derived from a CGA arginine mutation, is a critical therapeutic target in genetic medicine. This mutation occurs frequently at CpG dinucleotides, where cytosine deamination converts the sense CGA codon into a nonsense UGA codon [1.2.1, 1.2.5]. When this PTC enters the ribosomal A-site, it is recognized by eukaryotic release factors (eRF1/eRF3) rather than aminoacyl-tRNAs, leading to truncated protein products and the activation of nonsense-mediated mRNA decay (NMD) [1.2.2, 1.3.4]. This molecular event is a primary driver of approximately 11% of all human genetic diseases, including cystic fibrosis (e.g., G542X, R553X mutations) and Duchenne muscular dystrophy [1.3.3, 1.3.5]. In certain organisms like Saccharomyces cerevisiae, the CGA codon itself can be misdecoded as a stop codon due to inefficient tRNA competition, though this is less common in higher eukaryotes [1.1.2]. Pharmacological agents known as translational readthrough-inducing drugs (TRIDs), such as ELX-02 and ataluren, target the ribosomal A-site to decrease the fidelity of stop codon recognition [1.2.5, 1.3.1]. By promoting the incorporation of near-cognate tRNAs, these drugs allow the ribosome to read through the PTC and complete the synthesis of a full-length, functional protein [1.3.2, 1.3.4].

Other names

Nonsense codonPremature stop codonUGA nonsense codonCGA-derived nonsense mutationR-to-X mutation siteCGA nonsense codon

Translational readthrough induction (TRID) via binding to the ribosomal A-site to promote near-cognate tRNA incorporation over release factor binding.