Eukaryotic ribosome–release factor complex (eRF-ribosome complex)

The eukaryotic ribosome–release factor complex is a multi-component macromolecular assembly essential for the final stage of protein synthesis, known as translation termination (PNAS, 2014; NIH, 2021). This complex is primarily composed of the 80S ribosome and two key protein factors: eukaryotic release factor 1 (eRF1) and eukaryotic release factor 3 (eRF3, which includes isoforms GSPT1 and GSPT2) (Wikipedia, 2023; NIH, 2025). eRF1 acts as a molecular mimic of tRNA, recognizing stop codons (UAA, UAG, and UGA) in the ribosomal A-site and catalyzing the hydrolysis of the peptidyl-tRNA bond to release the completed polypeptide (NIH, 2023). eRF3 is a GTPase that associates with eRF1 and the ribosome to provide the energy and conformational changes necessary for efficient termination and subsequent ribosome recycling (PNAS, 2014; NIH, 2025). In the context of human disease, this complex has become a focal point for therapeutic intervention in oncology and genetic disorders (MDPI, 2024). In many cancers, particularly those driven by MYC oncogenes, cells become addicted to high rates of protein synthesis, making them hypersensitive to the degradation of eRF3 (GSPT1) via molecular glue degraders like MRT-2359 and CC-90009 (Monte Rosa Therapeutics, 2023; ACS, 2025). Conversely, in genetic diseases caused by nonsense mutations—such as cystic fibrosis and Duchenne muscular dystrophy—the complex is targeted by nonsense suppression agents like ataluren and aminoglycosides (NIH, 2024). These drugs interfere with the complex's accuracy, allowing the ribosome to read through premature stop codons and produce functional, full-length proteins (MDPI, 2024).

Other names

Eukaryotic translation termination complexeRF1-eRF3-ribosome complexPre-termination complex80S-eRF1-eRF3 complexRibosomal pre-termination complex

Targeted protein degradation of eRF3 (GSPT1) to disrupt translation in cancer cells; Promotion of stop codon read-through in nonsense suppression therapy.