Eukaryotic 28S ribosomal RNA sarcin–ricin loop (SRL)

The eukaryotic 28S ribosomal RNA sarcin–ricin loop (SRL) is a nearly universal and highly conserved 12-nucleotide RNA motif located in the large (60S) ribosomal subunit [PubMed: 8677602]. It serves as a critical docking site for translation elongation factors, specifically eEF-1 and eEF-2, and is essential for triggering the GTP hydrolysis required for tRNA translocation and ribosome movement along mRNA [PubMed: 31133953]. The SRL is famously the target of potent toxins known as Ribosome-Inactivating Proteins (RIPs), such as ricin from castor beans and Shiga toxins from bacteria [PubMed: 17113994]. These toxins act as N-glycosidases that specifically depurinate a single adenine residue (A4324 in humans) within the loop, while ribotoxins like alpha-sarcin cleave the phosphodiester backbone [PubMed: 20660480]. These modifications disrupt the interaction between the ribosome and elongation factors, leading to a complete and irreversible halt in protein synthesis and subsequent cell death [PubMed: 17113994]. Consequently, the SRL is a focal point in toxicology and is exploited in biotechnology to create targeted immunotoxins for cancer treatment [PubMed: 16648870].

Other names

Sarcin-ricin loopSRL28S rRNA SRLAlpha-sarcin loopSarcin/ricin domain

Ribosome-inactivating proteins (RIPs) target the SRL to either depurinate a specific adenine residue (N-glycosidase activity) or cleave the RNA backbone (ribonuclease activity), which irreversibly inhibits protein synthesis by preventing elongation factor binding [PubMed: 8677602, 17113994].