Sarcin-ricin loop of the 28S ribosomal RNA (SRL) (SRL)

The sarcin-ricin loop (SRL) is a highly conserved, 12-nucleotide sequence located within the 28S ribosomal RNA of the eukaryotic 60S ribosomal subunit (Garcia-Ortega et al., 2010). It serves as a critical functional center for protein synthesis, specifically facilitating the binding of translation elongation factors eEF1 and eEF2 and stimulating their essential GTPase activity (Shi et al., 2016). The SRL is the primary molecular target for Ribosome-Inactivating Proteins (RIPs), such as ricin, abrin, and Shiga toxin (Endo & Tsurugi, 1987). These toxins are often recruited to the SRL via interactions with the ribosomal P-stalk proteins (P0, P1, and P2), which guide the toxins to their site of action (Grela et al., 2019). Once at the SRL, RIPs typically function as N-glycosidases that depurinate a specific, universally conserved adenine residue, A4324 in humans (Endo & Tsurugi, 1987). This single modification irreversibly inactivates the ribosome by preventing elongation factor binding, leading to a rapid cessation of protein synthesis and subsequent cell death via apoptosis (Shi et al., 2016). In clinical research, this mechanism is exploited to develop immunotoxins, where RIPs are conjugated to antibodies to selectively eliminate malignant cells (Garcia-Ortega et al., 2010).

Other names

SRLAlpha-sarcin loop28S rRNA sarcin-ricin loopRicin/sarcin loopGTPase-associated center

Ribosome-inactivating proteins (RIPs) are recruited to the 60S subunit by the P-stalk proteins and subsequently depurinate the A4324 residue of the 28S rRNA sarcin-ricin loop, which sterically hinders the binding of elongation factors and halts translation.