Premature termination codon in mRNA within the ribosomal A site (PTC)

A premature termination codon (PTC) is a nonsense mutation in mRNA that prematurely signals the ribosome to stop translation, resulting in truncated, non-functional proteins and reduced mRNA stability through nonsense-mediated decay (NMD) (nih.gov, 2013). When a PTC enters the ribosomal A site, it is typically recognized by eukaryotic release factors (eRF1 and eRF3), which trigger the release of the nascent polypeptide (pnas.org, 2016). This specific molecular state—the PTC within the ribosomal A site—serves as a therapeutic target for nonsense suppression or "read-through" therapies (nih.gov, 2021). Small molecules like ataluren and certain aminoglycosides bind to the ribosome's decoding center to decrease the accuracy of codon recognition, thereby promoting the incorporation of a near-cognate aminoacyl-tRNA at the PTC (researchgate.net, 2020). This allows the ribosome to continue translation to the natural stop codon, restoring the production of full-length, functional proteins (nih.gov, 2020). This approach is a promising strategy for treating approximately 11% of all genetic diseases caused by nonsense mutations, including Duchenne muscular dystrophy and cystic fibrosis (nih.gov, 2021). However, therapeutic challenges include the potential for off-target read-through of legitimate stop codons and the varying efficiency of suppression depending on the specific stop codon and its surrounding sequence context (nih.gov, 2020).

Other names

Nonsense mutationPremature stop codonIn-frame premature termination codonPTC-ribosome complexPremature termination codon triplet

Nonsense suppression (translational read-through) by binding to the ribosomal decoding center to reduce the fidelity of codon-anticodon recognition, allowing the incorporation of near-cognate tRNAs at the premature stop codon site.