THE CONFORMATION OF THE SARCIN RICIN LOOP FROM 28S RIBOSOMAL-RNA

The sarcin/ricin loop is a highly conserved sequence found in the RNA of all large ribosomal subunits. The cytotoxins alpha-sarcin and ricin both inactivate ribosomes by cleaving a single bond in that loop. Onc e it has been attacked, ribosomes no longer interact with elongation f actors properly, and translation stops. We have determined the conform ation of the sarcin/ricin loop by multinuclear NMR spectroscopy using E73, a 29-nucleotide RNA that has the sarcin/ricin loop sequence and t hat is sensitive to both toxins in vitro. The sarcin/ricin loop has a compact structure that contains several purine.purine base pairs, a GA GA tetraloop, and a bulged guanosine adjacent to a reverse Hoogsteen A .U pair. It is stabilized by an unusual set of cross-strand base-stack ing interactions and imino proton to phosphate oxygen hydrogen bonds. In addition to having interesting structural features, this model expl ains many of the biochemical observations made about the loop's struct ure and its reactivity with cytotoxins, and it sheds light on the loop 's interactions with elongation factors.