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Transition metal complexes as probes for higher-order structure in RNA

Thesis/Dissertation ·
OSTI ID:5581076

A series of transition metal complexes was employed to examine higher-order structure in ribonucleic acids. The results indicate that the complexes Ru(phen)[sub 3][sup 2+], Ru(TMP)[sub 3][sup 2+], Rh(TMP)[sub 3][sup 3+], Rh(phen)[sub 2]phi[sup 3+], Rh(phi)[sub 2]bpy[sup 3+], and Rh(DIP)[sub 3][sup 3+] (phen = 1,10-phenanthroline; TMP = 3,4,7,8,-tetramethyl-1,10-phenanthroline; phi = 9,10-phenanthrenequinone diimine; bpy = bipyridyl; DIP = 4,7-diphenyl-1,10-phenanthroline) have different affinities for tRNA and bind RNA by several different modes of interaction. These differences in binding have been attributed to the different shapes of the metal complexes. Photolysis of the metal complexes promotes cleavage of native, structured RNA at diverse and novel sites with comparable efficiency and analogous product formation as found with cleavage of double-stranded DNA. As on DNA, RNA strand scission promoted by the complexes of rhodium(III) occurs through an oxidative pathway with the sugar moiety as the target. Reactions with the complexes of ruthenium(II) are consistent with mediation by singlet oxygen with the nucleic acid base as the target. The site selectivity associated with cleavage appears to be based upon the different binding properties. Ru(TMP)[sub 3][sup 3+] cleaves at a subset of solvent accessible sites cleaved by Ru(phen)[sub 3][sup 2+]. Different sites of cleavage on tRNA are apparent with the rhodium complexes, Rh(phen)[sub 2]phi[sup 3+], Rh(phi)[sub 2]bpy[sup 3+], and Rh(DIP)[sub 3][sup 3+], while Rh(TMP)[sub 3][sup 3+] does not promote strand scission of RNA. These shape-selective probes, which promote strand scission of tRNA at unique sites, have been applied to probe mutant tRNAs and to delineate the structure of 5S rRNA. This study demonstrates that small molecules can recognize distinct structures along an RNA strand and suggests that these structures may be utilized for specific recognition by proteins.

Research Organization:
California Inst. of Tech., Pasadena, CA (United States)
OSTI ID:
5581076
Country of Publication:
United States
Language:
English