Arginine-to-UGA premature termination codon (Arg-UGA PTC)

The Arginine-to-UGA premature termination codon (PTC) is a molecular target resulting from a nonsense mutation where an Arginine codon (typically CGA) is converted into a UGA stop signal in the mRNA. During translation, when this PTC reaches the ribosomal A-site, it causes the premature release of the nascent polypeptide chain, leading to truncated and usually unstable proteins. This specific mutation is prevalent in many genetic diseases because the C-to-T transition at CpG dinucleotides is a common mutational hotspot in the human genome, frequently affecting the Arginine CGA codon. Beyond protein truncation, these PTCs often trigger nonsense-mediated mRNA decay (NMD), a cellular surveillance mechanism that degrades the mutant mRNA, further exacerbating the protein deficiency. Therapeutic intervention focuses on small molecules known as read-through agents, which bind to the ribosome and alter its decoding sensitivity. These agents, such as ataluren or ELX-02, promote the insertion of a near-cognate tRNA at the UGA site, allowing the ribosome to continue translation to the natural stop codon and produce a functional, full-length protein.

Other names

Arg-TGA premature stop codonUGA nonsense mutationR-to-stop mutationPremature termination codon at the ribosomal A-siteCGA-to-TGA mutation

Induction of translational read-through by facilitating the incorporation of near-cognate aminoacyl-tRNAs at the premature stop codon site within the ribosomal A-site, bypassing the premature termination signal.