28S ribosomal RNA adenine 4324 (28S rRNA A4324)

28S ribosomal RNA adenine 4324 is a critical nucleotide located within the highly conserved sarcin/ricin loop (SRL) of the large (60S) ribosomal subunit in eukaryotes (Grela et al., 2019, Front Mol Biosci). This specific adenine residue serves as the primary substrate for ribosome-inactivating proteins (RIPs), such as ricin from Ricinus communis and Shiga toxins from Shigella dysenteriae (Endo & Tsurugi, 1987, J Biol Chem). These toxins possess RNA N-glycosidase activity, which allows them to specifically cleave the N-glycosidic bond at A4324, resulting in the depurination of the rRNA (Schramm, 2013, Chem Rev). The loss of this single adenine base irreversibly damages the SRL, preventing the binding of essential elongation factors (eEF-1 and eEF-2) and thereby halting protein synthesis (Walsh et al., 2013, Toxins). This molecular event triggers the ribotoxic stress response and leads to cell death via apoptosis, making it a significant factor in the pathology of certain bacterial infections and toxic exposures (Polito et al., 2016, Toxins). In biotechnology, this site is exploited by using RIPs as the cytotoxic payload in immunotoxins designed to target and destroy specific malignant cells (Potala et al., 2008, Drug Discov Today).

Other names

A4324Sarcin-ricin loop adenineSRL adenine28S rRNA depurination siteRicin target nucleotide

Ribosome-inactivating proteins (RIPs) act as site-specific RNA N-glycosidases that catalyze the hydrolytic cleavage of the N-glycosidic bond at adenine 4324. This depurination event disrupts the sarcin/ricin loop (SRL), which is essential for the binding of elongation factors eEF-1 and eEF-2, leading to the irreversible inhibition of protein synthesis and subsequent cell death (Endo & Tsurugi, 1987, J Biol Chem; Schramm, 2013, Chem Rev).