28S ribosomal RNA sarcin-ricin loop (SRL)

The 28S ribosomal RNA sarcin-ricin loop (SRL) is a highly conserved 12-nucleotide sequence in the large ribosomal subunit that is critical for protein synthesis (Endo & Tsurugi, 1987). It serves as the primary binding site for translational GTPases, such as elongation factors eEF-1 and eEF-2, which facilitate the movement of mRNA and tRNA through the ribosome (Shi et al., 2012). The SRL is the specific molecular target for Ribosome-Inactivating Proteins (RIPs), most notably the ricin A-chain (RTA) and Shiga toxins (Stx). These toxins function as RNA N-glycosidases that specifically depurinate the adenine residue at position A4324 in humans (Grela et al., 2019). This single modification prevents the binding of elongation factors, leading to a complete arrest of protein translation and subsequent cell death via apoptosis (Stirpe, 2004). Because of its essentiality and the extreme potency of the toxins that target it, the SRL is a major focus in toxicology and biodefense research. Additionally, the SRL-targeting mechanism is exploited in the development of immunotoxins, where RIPs are conjugated to antibodies for targeted cancer therapy (Walsh et al., 2013).

Other names

Sarcin-ricin loopSRLAlpha-sarcin loop28S rRNA adenine 4324Ricin-sarcin loop

N-glycosidase-mediated depurination of adenine A4324, which prevents the binding of elongation factors to the ribosome.