28S ribosomal RNA sarcin-ricin loop (SRL) (SRL)

The 28S ribosomal RNA sarcin-ricin loop (SRL) is a highly conserved RNA structural motif located in the large subunit of the eukaryotic ribosome (Endo et al., 1982). It is essential for protein synthesis, acting as the critical docking site for translation elongation factors EF-1 and EF-2 (Grela et al., 2014). The loop facilitates the interaction between the ribosome and these factors, triggering the GTP hydrolysis required for the translocation of tRNA and mRNA (Clementi et al., 2010). The SRL is the specific molecular target for ribosome-inactivating proteins (RIPs), such as ricin from castor beans and Shiga toxins from certain bacteria (Endo et al., 1987). These toxins function as RNA N-glycosidases that remove a specific adenine residue (A4565 in humans) from the loop, or as endonucleases like alpha-sarcin that cleave the RNA backbone (Stirpe, 2004). Such modifications prevent the binding of elongation factors, leading to the immediate and irreversible cessation of translation (Endo et al., 1987). Because of its vital role, the SRL is a focal point in toxicology and the development of targeted cancer therapies (Stirpe, 2004). Therapeutic strategies often involve conjugating RIPs to monoclonal antibodies to create immunotoxins that selectively deliver the toxin to malignant cells (Stirpe, 2004). Understanding the SRL's structure and function is crucial for developing antidotes to RIP poisoning and improving the efficacy of toxin-based drugs (Grela et al., 2014).

Other names

Sarcin-ricin loopSRLAlpha-sarcin loopRicin loop28S rRNA SRL

Inhibition of translation elongation by preventing elongation factor binding through site-specific RNA modification (depurination or cleavage).