Ribosomal translation termination machinery at premature stop codons (PTC termination machinery)

The ribosomal translation termination machinery at premature stop codons (PTCs) is a complex system involving the ribosome and eukaryotic release factors, primarily eRF1 and eRF3, which recognize stop signals in mRNA (Keeling et al., 2014). In genetic diseases caused by nonsense mutations, a PTC is introduced prematurely, leading to truncated, non-functional proteins and mRNA degradation via nonsense-mediated decay (NMD) (Bidou et al., 2012). This machinery is a therapeutic target for "read-through" drugs, such as ataluren and aminoglycosides, which decrease the fidelity of the ribosome at the PTC (Welch et al., 2007). By encouraging the incorporation of a near-cognate tRNA instead of termination factors, these drugs allow the ribosome to continue translation to the end of the transcript (Peltz et al., 2013). This process restores the production of full-length, functional proteins, offering a potential treatment for a wide range of inherited disorders including cystic fibrosis and Duchenne muscular dystrophy (Linde and Kerem, 2008).

Other names

Premature termination codon machineryNonsense mutation suppression machineryRibosomal read-through complexPTC-mediated termination complex

Translational read-through induction via suppression of premature termination codons (PTCs). Drugs bind to the ribosome's decoding center or peptidyl transferase center, reducing the accuracy of codon-anticodon pairing. This allows the incorporation of a near-cognate tRNA at the PTC, enabling the ribosome to continue translation to the natural stop codon and produce a full-length protein (Keeling et al., 2014; Welch et al., 2007).