28S ribosomal RNA sarcin–ricin loop (SRL)

The 28S ribosomal RNA sarcin–ricin loop (SRL) is a nearly universal and highly conserved 12-nucleotide RNA motif located within Domain VI of the large (60S) ribosomal subunit in eukaryotes (Correll et al., 1998). It serves as a critical functional center for protein synthesis, acting as the primary docking site for translation elongation factors eEF1A and eEF2. The SRL is essential for stimulating the GTPase activity of these factors, a process required for tRNA delivery and ribosomal translocation (Voorhees et al., 2010). This loop is the specific target of potent Ribosome-Inactivating Proteins (RIPs) like ricin and ribotoxins like alpha-sarcin. Ricin removes a specific adenine base (A4324), while alpha-sarcin cleaves the RNA backbone; both actions prevent elongation factor binding and lead to a complete cessation of cellular protein synthesis (Endo & Tsurugi, 1987). Due to its vital role in cell survival and its susceptibility to specific toxins, the SRL is a major focus in toxicology and is exploited in the development of targeted immunotoxins for treating malignancies (Stirpe, 2004).

Other names

Sarcin-ricin loopSRLAlpha-sarcin loopRicin-sarcin loop28S rRNA SRLA-site finger

Ribosome-inactivating proteins (RIPs) and ribotoxins target the SRL to irreversibly inhibit protein synthesis. Type II RIPs, such as ricin, function as highly specific RNA N-glycosidases that depurinate the A4324 residue in the 28S rRNA (Endo et al., 1987). Ribotoxins like alpha-sarcin act as specific endonucleases, cleaving the phosphodiester bond between G4325 and A4326 (Wool et al., 1992). Both modifications disrupt the structural integrity of the SRL, preventing the binding of elongation factors eEF1A and eEF2 and the stimulation of their GTPase activity, which effectively halts the translation process.