Structure-function correlation of disease-related functional RNA

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Vault particle is related to multi-drug resistance. We found that RNA component of the vault (vault RNA)binds to anti-cancer drug, mitoxantrone. On the basis of chemical shift perturbation with NMR, we found that vault RNA binds to several other anti-cancer drugs. The binding site for drugs was also identified. By blocking the binding site with its complementary oligonucleotide, the trap of drugs by vault. RNA may be suppressed, which could lead to the overcome of the multi-drug resistance.The aptamer composed of RNA containing the Rev-responsive element and the Rev peptide was developed by our collaborator, Professor Morii of Kyoto University. We analyzed the structure of this aptamer in complex with its ligand. The formation of new hydrogen bonds was observed for RNA upon the binding of the Rev peptide and the ligand, respectively. The secondary structure of RNA was deduced. The structure determination of the aptamer is in progress.It was reported that DNA composed of the 4'-thiodeoxyriboses, 4'-thioDNA, exhibits remarkable features. Particularly, 4'-thioDNA is resistant to cleavage by DNase I. We determined the structure of 4'-thioDNA by NMR. DNA usually takes on B-form. 4'-thioDNA, however, takes on A-form which is the form for RNA. DNase I binds to DNA through the interaction at the narrow and relatively deep minor groove of the B-form. The minor groove of 4'-thioDNA is wide and shallow, which is characteristic to A-form, and is not suitable for the binding of DNase I. The other remarkable features of 4'-thioDNA were also interpreted on the basis of the determined structure.