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Eukaryotic 28S ribosomal RNA (28S rRNA) is the structural and catalytic core of the eukaryotic 60S large ribosomal subunit, serving as a ribozyme that facilitates the peptidyl transferase reaction during protein synthesis (NCBI, 2023). It features a highly conserved region known as the sarcin/ricin loop (SRL), which is essential for the binding of translation elongation factors eEF-1 and eEF-2 (PubMed, PMID: 11554172). This loop is the primary target for Ribosome-Inactivating Proteins (RIPs) like ricin and Shiga toxin, which irreversibly depurinate a specific adenine residue, thereby halting translation and inducing cell death (UniProt, P02879). Beyond its role in translation, 28S rRNA acts as a sensor for cellular stress; damage to its structure triggers the ribotoxic stress response, activating signaling cascades such as the p38 and JNK MAPK pathways (PubMed, PMID: 15688010). In a therapeutic context, 28S rRNA is targeted by experimental immunotoxins designed to deliver RIPs specifically to malignant cells (StatPearls, NBK557574). Its dysregulation is also increasingly recognized in the context of ribosomopathies and oncogenesis, where altered rRNA processing can drive disease progression (PubMed, PMID: 30639201). Furthermore, certain antibiotics and small molecules can bind to the peptidyl transferase center of the 28S rRNA to inhibit protein synthesis in eukaryotic cells or specific organelles (PubChem, CID 2520).
Site-specific depurination of the sarcin/ricin loop (SRL) by N-glycosidases or competitive inhibition of the peptidyl transferase center, leading to the cessation of protein synthesis (PubMed, PMID: 11554172; PubChem, CID 2520).
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