Eukaryotic 28S ribosomal RNA (28S rRNA) (28S rRNA)

The eukaryotic 28S ribosomal RNA (rRNA) is the structural and catalytic core of the large (60S) ribosomal subunit in eukaryotic cells. It contains the peptidyl transferase center (PTC), a highly conserved ribozyme responsible for catalyzing peptide bond formation during translation (Polacek & Mankin, 2005, PubMed). The 28S rRNA is a critical target for various Ribosome-Inactivating Proteins (RIPs) such as ricin and Shiga toxins, which irreversibly depurinate the sarcin/ricin loop (SRL) to halt protein synthesis (Grela et al., 2019, Frontiers in Chemistry). Additionally, the PTC within the 28S rRNA is the binding site for the FDA-approved drug Omacetaxine mepesuccinate, which inhibits the initial step of protein elongation (Gandhi et al., 2014, Blood). While most antibiotics target bacterial ribosomes, the eukaryotic 28S rRNA is increasingly explored for targeted cancer therapies and as a marker for ribosomopathies (Sulima et al., 2017, British Journal of Cancer). Dysregulation of this target is associated with nucleolar stress and the activation of the p53 pathway, making it a significant focus in both toxicology and oncology. Therapeutic challenges include the high systemic toxicity of 28S rRNA inhibitors and the potential for immunogenicity when using toxin-conjugated antibodies.

Other names

28S rRNALarge subunit ribosomal RNALSU rRNA28S ribosomal RNA component of the 60S subunitRNA, 28S ribosomal

Inhibition of protein synthesis through the catalytic inactivation of the peptidyl transferase center or the site-specific depurination of the sarcin/ricin loop.