Eukaryotic 60S ribosomal subunit 28S rRNA sarcin–ricin loop (SRL)

The eukaryotic 60S ribosomal subunit 28S rRNA sarcin–ricin loop (SRL) is a highly conserved, 12-nucleotide RNA structure located within the large ribosomal subunit that is essential for protein synthesis (Grela et al., 2019, Molecules). It functions as a critical docking site for translation elongation factors (eEF-1 and eEF-2) and is necessary for the activation of their GTPase activity, which drives the translocation step of translation (Endo & Wool, 1982, JBC). The SRL is the specific molecular target for Ribosome-Inactivating Proteins (RIPs) such as ricin, which acts as an N-glycosidase to remove a specific adenine residue (A4324 in humans), and alpha-sarcin, which cleaves the phosphodiester bond between G4325 and A4326 (Stirpe & Battelli, 2006, CMLS). These covalent modifications prevent elongation factors from binding, effectively halting protein synthesis and triggering apoptosis. In a clinical context, the SRL is targeted by experimental immunotoxins, where RIPs are conjugated to monoclonal antibodies to treat various cancers by inducing selective cell death (Walsh et al., 2013, Toxins).

Other names

Sarcin-ricin loopSRL28S rRNA sarcin-ricin domainAlpha-sarcin loopA4324 loop

Ribosome-inactivating proteins (RIPs) target the SRL through either N-glycosidase activity, which depurinates a specific adenine (e.g., ricin, Shiga toxin), or ribonuclease activity, which cleaves a specific phosphodiester bond (e.g., alpha-sarcin). These modifications disrupt the binding and GTPase activation of elongation factors eEF-1 and eEF-2, leading to the irreversible inhibition of protein synthesis (Grela et al., 2019, Molecules; Endo & Wool, 1982, JBC).