Eukaryotic ribosome 28S rRNA sarcin–ricin loop (SRL) (SRL)

The Eukaryotic ribosome 28S rRNA sarcin–ricin loop (SRL) is a highly conserved 12-nucleotide RNA motif located within the large (60S) ribosomal subunit that is essential for the elongation phase of protein synthesis (Grela et al., 2019, Int J Mol Sci). It serves as a critical docking and activation site for translational GTPases, including elongation factors eEF1A and eEF2, which are required for aminoacyl-tRNA selection and ribosomal translocation (Shi et al., 2012, J Mol Biol). The SRL is the primary molecular target for potent Ribosome-Inactivating Proteins (RIPs) such as ricin, abrin, and Shiga toxins, which irreversibly damage the loop by removing a specific adenine base (depurination) (Stirpe & Battelli, 2006, Cell Mol Life Sci). Other agents, like the fungal ribotoxin alpha-sarcin, catalyze a specific endonucleolytic cleavage within the loop (Endo & Wool, 1982, J Biol Chem). These modifications prevent the ribosome from interacting with elongation factors, leading to a total cessation of protein synthesis and subsequent cell death. In pharmaceutical development, the SRL is targeted indirectly via immunotoxins, which utilize the catalytic domains of these toxins conjugated to antibodies to selectively destroy cancer cells (Walsh et al., 2013, Toxins).

Other names

Sarcin-ricin loopSRL28S rRNA sarcin-ricin domainAlpha-sarcin loopH95 loop

Ribosome-inactivating proteins (RIPs) target the SRL to inhibit protein synthesis. Type I and II RIPs, such as ricin and abrin, function as RNA N-glycosidases that specifically depurinate the A4324 residue in the human 28S rRNA (Stirpe & Battelli, 2006, Cell Mol Life Sci). Ribotoxins, such as alpha-sarcin, act as site-specific endonucleases that cleave the phosphodiester bond between G4325 and A4326 (Endo & Wool, 1982, J Biol Chem). Both types of modifications prevent the binding of elongation factors eEF1A and eEF2 to the ribosome, thereby halting the translocation step of translation and inducing apoptosis (Shi et al., 2012, J Mol Biol).