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

The 28S ribosomal RNA adenine-4324 is a critical nucleotide located within the highly conserved sarcin/ricin loop (SRL) of the eukaryotic large ribosomal subunit. This specific adenine residue is essential for the binding of translation elongation factors, such as eEF-1 and eEF-2, which facilitate the translocation step of protein synthesis (Endo & Tsurugi, 1987). It is the primary target for Type II ribosome-inactivating proteins (RIPs), most notably ricin and Shiga toxins. These toxins function as RNA N-glycosidases that specifically cleave the N-glycosidic bond of A4324, removing the adenine base and rendering the ribosome unable to interact with elongation factors (Szewczak & Moore, 1995). This irreversible modification leads to the complete cessation of cellular protein synthesis and subsequent cell death via apoptosis. While primarily known as a target for potent biological toxins, this site is also exploited in the development of immunotoxins for cancer therapy, where toxin subunits are conjugated to antibodies to selectively deplete malignant cells (Walsh et al., 2013).

Other names

Sarcin/ricin loop adenineSRL A4324Ricin target siteA4324 of 28S rRNADepurination site of 28S rRNA

RNA N-glycosidase mediated depurination of the adenine base at position 4324, which prevents the binding of elongation factors and irreversibly inhibits protein synthesis.