Eukaryotic translation termination machinery (eRF complex)

The eukaryotic translation termination machinery is a multi-protein complex essential for the final phase of mRNA translation, ensuring the accurate release of nascent polypeptides from the ribosome. The primary components are eukaryotic release factor 1 (eRF1), which acts as a tRNA mimic to recognize stop codons (UAA, UAG, and UGA) in the ribosomal A-site, and eukaryotic release factor 3 (eRF3), a GTPase that provides the energy required for peptide release (UniProt P62495, P15170). This machinery is a significant therapeutic target for treating genetic diseases caused by nonsense mutations, which account for approximately 11% of all described human gene lesions (PubMed 22135353). Pharmacological agents such as ataluren and aminoglycosides target this complex to induce “read-through” of premature termination codons (PTCs), enabling the production of full-length, functional proteins in diseases like Duchenne muscular dystrophy and cystic fibrosis (PubMed 17476335). However, therapeutic development is complicated by the need to selectively target PTCs while avoiding the read-through of natural stop codons, which could lead to toxic protein extensions (PubMed 24558141).

Other names

Eukaryotic release factor complexTranslation termination complexeRF1-eRF3 complex

Induction of premature termination codon (PTC) read-through by promoting the insertion of near-cognate aminoacyl-tRNAs at stop codons, thereby bypassing nonsense mutations and restoring full-length protein production.