NMR analysis of a loop-bulge structure of UUCGA pentaloop.

Although structures of many RNA loops, such as GNRA and UNCG tetraloops, were well known, it is still possible to find more RNA structures. In the present study, solution structure of an RNA fragment having UUCGA pentaloop was analyzed by NMR spectroscopy. It was found that the UUCG tetraloop is formed and the adenosine residue at the 3' side of the tetraloop is bulged out. The characteristic motif of the loop-bulge structure has also been found in other RNAs including CUUGU and CUGGC pentaloops. Along with the recently found T-hairpin structure with a UUUGAUU loop, in which UUUGA pentaloop and UU bulge are formed, the loop-bulge structures can be categorized as an RNA motif and it may be called as the integrated structure loop, I-loop.

Interaction between a fluoroquinolone derivative KG022 and RNAs: Effect of base pairs 3' adjacent to the bulged residues.

RNA-targeted small molecules are a promising modality in drug discovery. Recently, we found that a fluoroquinolone derivative, KG022, can bind to RNAs with bulged C or G. To clarify the RNA specificity of KG022, we analyzed the effect of the base pair located at the 3'side of the bulged residue. It was found that KG022 prefers G-C and A-U base pairs at the 3'side. Solution structures of the complexes of KG022 with the four RNA molecules with bulged C or G and G-C or A-U base pairs at the 3'side of the bulged residue were determined to find that the fluoroquinolone moiety is located between two purine bases, and this may be the mechanism of the specificity. This work provides an important example of the specificity of RNA-targeted small molecules.