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Structure-function correlation of disease-related functional RNA

疾病相关功能RNA的结构-功能相关性

基本信息

批准号：
18370046
负责人：
KATAHIRA Masato
金额：
$ 9.8万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18370046/
关键词：
multi-drug resistance anti-cancer dru aptamer Rev 4'-thioDNA Vault C型肝炎構造 IRES 薬剤耐性 NMR RNA

项目摘要

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.

Vault颗粒与多重耐药有关。我们发现穹窿体的RNA成分（穹窿体RNA）与抗癌药物米托蒽醌结合。基于 NMR 化学位移扰动，我们发现穹窿 RNA 与其他几种抗癌药物结合。还确定了药物的结合位点。通过与其互补的寡核苷酸阻断结合位点，药物被拱顶捕获。 RNA可能被抑制，从而克服多重耐药性。由含有Rev响应元件的RNA和Rev肽组成的适配体是由我们的合作者、京都大学的森井教授开发的。我们分析了该适体与其配体复合物的结构。在 Rev 肽和配体结合后，分别观察到 RNA 形成新的氢键。推导了RNA的二级结构。该适配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DNA，表现出显着的特征。特别是，4'-thioDNA 能够抵抗 DNase I 的切割。我们通过 NMR 确定了 4'-thioDNA 的结构。 DNA通常呈B型。然而，4'-thioDNA 呈 A 型，即 RNA 的形式。 DNase I 通过 B 型狭窄且相对较深的小沟处的相互作用与 DNA 结合。 4'-thioDNA的小沟又宽又浅，这是A型的特征，不适合DNase I的结合。4'-thioDNA的其他显着特征也根据确定的结构进行了解释。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Wild and mutant (phosphorylation-mimicking) GT-1 structures, hnRNP D-telomere DNA complex structure, and Musashi structure complexed with RNA

野生型和突变型（模拟磷酸化）GT-1 结构、hnRNP D-端粒 DNA 复合物结构以及与 RNA 复合的 Musashi 结构

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Ohyama;T.;Tsuchibayashi;H.;Matsugami;A.;Miyanoiri;Y.;Niyada;E.;Enokizono;Y.;Nagata;T.;Katahira;M
通讯作者：
M

Interactions with RNA/DNA of proteins involved in the regulation of transcription, translation and telomere elongation.

参与转录、翻译和端粒延长调节的蛋白质与 RNA/DNA 的相互作用。

DOI：
发表时间：
2007
期刊：
Nucleic Acids Symp Ser (Oxf). (51)
影响因子：
0
作者：
Ohyama T;Furukawa A;Miyoshi T;Takada Y;Ohgara S;Hiratsuka K;Imai T;Okano H;Nakagama H;Nagata T;Katahira M.
通讯作者：
Katahira M.

Molecular mechanism for maintenance of G-rich short tandem repeats capable of adopting G4 DNA structures

维持能够采用G4 DNA结构的富含G的短串联重复序列的分子机制