N(6)-Methyladenine hinders RNA- and DNA-directed DNA synthesis: application in human rRNA methylation analysis of clinical specimens.
N(6)-Methyladenine hinders RNA- and DNA-directed DNA synthesis: application in human rRNA methylation analysis of clinical specimens.
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N-6-甲基腺嘌呤阻碍 RNA 和 DNA 指导的 DNA 合成：在临床标本的人 rRNA 甲基化分析中的应用
DOI：
10.1039/c5sc02902c
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发表时间：
2016-02-01
期刊：
影响因子：
8.4
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Wang S;Wang J;Zhang X;Fu B;Song Y;Ma P;Gu K;Zhou X;Zhang X;Tian T;Zhou X
N-6-甲基腺嘌呤(M6A)是哺乳动物基因中含量最丰富的内部修饰。最近，m6A被报道为真核生物中一个潜在的重要的表观遗传标记。到目前为止，对m6A进行特定部位的检测在技术上非常具有挑战性。在这里，我们首先揭示了m6A显著阻碍DNA和RNA指导的DNA合成。对各种5-取代2‘-脱氧尿苷类似物的5’-三磷酸进行了系统的研究。在目前的研究中，利用BST DNA聚合酶催化的引物延伸，已经实现了对RNA或DNA背景下m6A的定量分析。分子动力学研究预测，模板中的m6A倾向于进入并抑制BST DNA聚合酶的MGR区，降低DNA骨架的构象灵活性。更重要的是，提供了一种高精度的人核糖体RNA(RRNA)中m6A的定点测定方法。通过对甲基化改变的累积分析，我们首先揭示了在肝细胞癌患者中存在与癌症相关的显著的人类rRNA甲基化改变。在这里，我们报告了m6A显著阻碍DNA和RNA诱导的DNA合成，并已实现了在RNA或DNA背景下对m6A的定量分析。
N 6-Methyladenine (m6A) is the most abundant internal modification on mammalian mRNA. Very recently, m6A has been reported as a potentially important ‘epigenetic’ mark in eukaryotes. Until now, site-specific detection of m6A is technically very challenging. Here, we first reveal that m6A significantly hinders DNA- and RNA-directed DNA synthesis. Systematic investigations of 5′-triphosphates of a variety of 5-substituted 2′-deoxyuridine analogs in primer extension have been performed. In the current study, a quantitative analysis of m6A in the RNA or DNA context has been achieved, using Bst DNA polymerase catalyzed primer extension. Molecular dynamics study predicted that m6A in template tends to enter into and be restrained in the MGR region of Bst DNA polymerase, reducing conformational flexibility of the DNA backbone. More importantly, a site-specific determination of m6A in human ribosomal RNA (rRNA) with high accuracy has been afforded. Through a cumulative analysis of methylation alterations, we first reveal that significantly cancer-related changes in human rRNA methylation were present in patients with hepatocellular carcinoma. Here, we report that m6A significantly hinders DNA- and RNA-directed DNA synthesis, and a quantitative analysis of m6A in RNA or DNA context has been achieved..
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N6-甲基脱氧腺苷标记了衣原体中的主动转录起始位点。
影响因子：
64.5
作者：
Fu Y;Luo GZ;Chen K;Deng X;Yu M;Han D;Hao Z;Liu J;Lu X;Dore LC;Weng X;Ji Q;Mets L;He C
通讯作者：
He C
DOI：
10.1186/bcr3375
发表时间：
2013-01-15
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Kloten V;Becker B;Winner K;Schrauder MG;Fasching PA;Anzeneder T;Veeck J;Hartmann A;Knüchel R;Dahl E
通讯作者：
Dahl E
影响因子：
15
作者：
Harcourt EM;Ehrenschwender T;Batista PJ;Chang HY;Kool ET
通讯作者：
Kool ET
影响因子：
4.1
作者：
Lee, Bongyong;Mazar, Joseph;Perera, Ranjan J.
通讯作者：
Perera, Ranjan J.
DOI：
10.1126/science.1151710
发表时间：
2007-11-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gerken T;Girard CA;Tung YC;Webby CJ;Saudek V;Hewitson KS;Yeo GS;McDonough MA;Cunliffe S;McNeill LA;Galvanovskis J;Rorsman P;Robins P;Prieur X;Coll AP;Ma M;Jovanovic Z;Farooqi IS;Sedgwick B;Barroso I;Lindahl T;Ponting CP;Ashcroft FM;O'Rahilly S;Schofield CJ
通讯作者：
Schofield CJ