Eukaryotic ribosome translation termination machinery (Ribosome-PTC complex)

The eukaryotic ribosome and its associated translation termination machinery serve as a critical therapeutic target for genetic diseases caused by nonsense mutations. These mutations introduce premature termination codons (PTCs) into mRNA, leading to truncated, non-functional proteins and often triggering nonsense-mediated mRNA decay (NMD). The termination machinery primarily involves the eukaryotic release factors eRF1 and eRF3, which recognize stop codons in the ribosomal A-site and facilitate polypeptide release. Drugs targeting this complex, such as ataluren and certain aminoglycosides, modulate the ribosome's decoding center to favor 'read-through'—the insertion of a near-cognate amino acid instead of termination. This allows the translation of a full-length protein that can restore biological function in patients with conditions like Duchenne muscular dystrophy or cystic fibrosis. While promising, the primary challenge lies in achieving selective read-through at PTCs without affecting the natural termination codons required for normal cellular function.

Other names

Eukaryotic translation termination complexRibosomal read-through machineryPremature termination codon (PTC) complexNonsense mutation suppression machinery

Small molecules interact with the eukaryotic ribosome at the decoding center to promote the insertion of a near-cognate tRNA at premature stop codons (PTCs), thereby bypassing the termination signal and allowing the synthesis of a full-length, functional protein.