Mechanisms for quality control of RNA in mammalian cells

哺乳动物细胞 RNA 质量控制机制

• 批准号: 18370005
• 负责人: SEKIGUCHI Mutsuo
• 金额: $ 11万
• 依托单位: Fukuoka Dental College
• 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-18370005/
• 关键词: oxidative stress; RNA; oxidized guanine; ribonucleotide; mouse; quality control; genetic information; expression

The basal level of spontaneous errors in RNA synthesis is estimated to be 10^<-5> per residue, which is considerably higher than that for DNA replication, and the fidelity of transcription would be worse in an aerobic state. This means that numerous erroneous proteins are synthesized even in normal cells. Furthermore, the transcriptional fidelity would become lower when the RNA bases are modified by internal or external agents. Among such modifications, 8-oxoguanine (8-oxoG) is particularly important since this modified base causes base mispairing. It has been shown that the incorporation of 8-oxoG opposite the adenine residues of DNA by RNA polymerase causes a partial phenotypic suppression. In this case, although the majority of the proteins made are normal, some of the products are abnormal. Most of the erroneous proteins produced may be inactive, but some may exhibit dominant characteristics that can cause disorders of some cellular functions, which could thus lead to catastrophic consequences.8-oxoG can be formed in RNA by the incorporation of oxidized guanine nucleotide into RNA and also by the direct oxidation of the constituent guanine base in the RNA. In E coli, the MutT protein functions to prevent the former process while the PNP protein appears to be involved in the latter. Similar mechanisms seem to function in mammalian cells, but the situations are much more complex in comparison to the bacterial ones. At least two proteins with different substrate preferences, MTH1 and NUDT5, are involved in the former process, and also two different types of proteins, PNP and YB-1, are implicated with the latter process.

RNA合成中自发性误差的基础水平估计为每个残基10^<-5>，它大大高于DNA复制，在有氧态下，转录的保真度会更糟。这意味着即使在正常细胞中也合成了许多错误的蛋白质。此外，当RNA碱基被内部或外部试剂修饰时，转录保真度将变得较低。在此类修改中，8-氧气（8-oxog）尤为重要，因为这种修饰的基础会导致基础错误。已经表明，RNA聚合酶与DNA的腺嘌呤残基相反的8-氧化物会导致部分表型抑制。在这种情况下，尽管大多数蛋白质制成的大多数都是正常的，但其中一些产品是异常的。产生的大多数错误蛋白可能是无活跃的，但是有些可能表现出可能引起某些细胞功能的疾病的主要特征，因此可能导致灾难性后果。8-OXOG可以通过将氧化的鸟嘌呤核苷酸掺入RNA中形成RNA，并通过将氧化核苷酸掺入RNA中，并通过直接氧化为RNA，并通过直接氧化氧化氧化和氧化。在e大肠杆菌中，杂种蛋白的功能可预防前一种过程，而PNP蛋白似乎参与了后者。相似的机制似乎在哺乳动物细胞中起作用，但是与细菌相比，情况更为复杂。至少有两个具有不同底物偏好的蛋白质MTH1和NUDT5参与了以前的过程，并且两种不同类型的蛋白质PNP和YB-1与后一个过程有关。

项目成果

アルキル化損傷細胞にアポトーシスを誘導する新規遺伝子の同定

诱导烷基化损伤细胞凋亡的新基因的鉴定

• 发表时间: 2007
• 作者: 日高真純;他
• 通讯作者: 他

Modes of action of two types of anti-neoplastic drugs,dacarbnazine and ACNU,to induce apoptosis

达卡嗪和ACNU两类抗肿瘤药物诱导细胞凋亡的作用方式

• 发表时间: 2007
• 期刊: Carcinogenesis 28
• 作者: K.Shirasaki;T.Yamamura;Y.Monden;Y.Shiokawa;Masayuki Sanada
• 通讯作者: Masayuki Sanada

アルキル化発がんを抑制するアポトーシスの機構

细胞凋亡机制抑制烷基化致癌作用

• 发表时间: 2006
• 作者: Hiroshi Hayakawa;Ja-Eun Kim;Mutsuo Sekiguchi;Mutsuo Sekiguchi;Mutsuo Sekiguchi;Mutsuo Sekiguchi;Ja-Eun Kim;有森 貴夫;日高 真純;有森 貴夫;Masumi Hidaka;Mutsuo Sekiguchi;Nlasumi Hidaka;Mutsuo Sekiguchi;日高 真純;Masumi Hidaka;Mutsuo Sekiguchi;Masumi Hidaka;Mutsuo Sekiguchi;Nlaumi Hidaka;Mutsuo Sekiguchi;Hiroshi Hayakawa;Mutsuo Sekiguchi;Hiroshi Hayakawa;高木 康光;真田 正幸;高木 康光
• 通讯作者: 高木 康光

Modes of action of two types of anti-neoplastic drugs, dacarbnazine and ACNU, to induce aotosis

达卡嗪和 ACNU 两类抗肿瘤药物诱导耳鸣的作用方式

• 发表时间: 2007
• 期刊: Carcinogenesis 28
• 作者: K.Shirasaki;T.Yamamura;Y.Monden;Y.Shiokawa;Masayuki Sanada;Masayuki Sanada;Masayuki Sanada
• 通讯作者: Masayuki Sanada

Molecular devices for high fidelity of DNA replication and gene expression.

• DOI: 10.2183/pjab.82.278
• 发表时间: 2006-12
• 期刊: Proceedings of the Japan Academy. Series B, Physical and biological sciences
• 作者: Sekiguchi M