28S ribosomal RNA (A3560 and A4045 in the peptidyl transferase center) (28S rRNA (PTC))

The 28S ribosomal RNA (28S rRNA) is the structural and catalytic core of the eukaryotic large ribosomal subunit (60S), playing a fundamental role in protein synthesis (UniProt, 2024). Within the 28S rRNA, the peptidyl transferase center (PTC) is the active site responsible for catalyzing peptide bond formation between amino acids. Specific adenine residues within the PTC, notably A3560 and A4045 (human/rat numbering), are essential for the proper orientation of tRNA molecules and the catalytic activity of the ribosome (Brigotti et al., 2002). These residues are the primary or secondary targets of various Ribosome-Inactivating Proteins (RIPs), such as Saporin-S6 and Gelonin, which function as RNA N-glycosidases to remove the adenine base (depurination) (Barbieri et al., 1993). This irreversible modification halts translation and triggers the ribotoxic stress response, leading to apoptosis via the activation of JNK and p38 MAPK pathways (Pestka, 2010). In biotechnology, these sites are exploited through the development of immunotoxins, where RIPs are conjugated to antibodies to selectively target and kill cancer cells (Polito et al., 2013).

Other names

Large subunit ribosomal RNA28S rRNAPeptidyl transferase centerPTCrRNA N-glycosidase target60S ribosomal RNA

Inhibition of protein synthesis through the depurination of A3560 and A4045 residues by RNA N-glycosidases (such as Saporin), or through the competitive binding of small molecules to the PTC, which prevents peptide bond formation and induces the ribotoxic stress response (Brigotti et al., 2002; Pestka, 2010).