Structure-function correlation of disease-related functional RNA

拱顶颗粒与多药耐药有关。我们发现拱顶的RNA成分（拱顶RNA）与抗癌药物米托蒽醌结合。基于核磁共振的化学位移扰动，我们发现vault RNA与其他几种抗癌药物结合。药物的结合位点也被确定。通过用其互补的寡核苷酸阻断结合位点，使药物的陷阱跳顶。RNA可能被抑制，从而克服多重耐药。该核酸适体由含有Rev响应元件和Rev肽的RNA组成，由我们的合作者京都大学Morii教授开发。我们分析了该适体与其配体的配合物结构。在Rev肽和配体结合时，分别观察到RNA形成新的氢键。推导出了RNA的二级结构。适体的结构测定正在进行中。据报道，由4'-硫代脱氧核糖组成的DNA，即4'-硫代脱氧核糖，具有显著的特征。特别是，4′-硫代核糖核酸（4′-thioDNA）具有抗dna酶i切割的能力。DNA通常呈b型。然而，4'-硫代脱氧核糖核酸呈a型，这是RNA的形式。DNA酶I通过b型狭窄而较深的小凹槽的相互作用与DNA结合。4'-thioDNA的小凹槽宽而浅，呈a型特征，不适合与DNase i结合。4'-thioDNA的其他显著特征也在确定结构的基础上进行了解释。

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.