Eukaryotic ribosome and translation machinery

The eukaryotic ribosome and translation machinery is the multi-component system responsible for synthesizing proteins from messenger RNA (mRNA) templates. It consists of the 80S ribosome (comprising 40S and 60S subunits), various eukaryotic initiation factors (eIFs), elongation factors (eEFs), and release factors. This machinery is frequently exploited by viruses to prioritize the synthesis of viral proteins over host proteins, and its dysregulation is a hallmark of many cancers where increased translation of oncogenes supports rapid cell proliferation (Bushell & Sarnow, 2002; Ruggero, 2013). Therapeutic strategies targeting this apparatus include the use of small molecules like omacetaxine mepesuccinate, which inhibits the elongation phase by preventing the correct positioning of aminoacyl-tRNA, and newer agents like zotatifin that target the eIF4A helicase to prevent the assembly of the translation initiation complex (Gandhi et al., 2014; Ernst et al., 2020). While effective in specific contexts like chronic myeloid leukemia or certain solid tumors, targeting the host's fundamental protein synthesis machinery carries a high risk of systemic toxicity, particularly myelosuppression, due to the essential nature of translation in all healthy cells (Robin et al., 2014).

Other names

Host ribosome80S ribosomeHost translational apparatusProtein synthesis machineryEukaryotic translation system

Inhibition of the peptidyl transferase center, disruption of the eIF4F initiation complex, inhibition of eIF4A RNA helicase activity, or site-specific depurination of 28S rRNA.