AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation
AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation
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DOI：
10.1016/j.molcel.2004.09.002
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发表时间：
2004-10-08
期刊：
影响因子：
16
通讯作者：
Falnes, PO
中科院分区：
文献类型：
--
作者：
Ougland, R;Zhang, CM;Falnes, PO
通过甲基化试剂将有害的1-甲基腺嘌呤（1-meA）和3-甲基胞嘧啶（3-meC）损伤引入核酸中。最近的研究表明，E.大肠杆菌AlkB蛋白和人类同源物hABH 3可以使这些DNA和RNA中的损伤去甲基化。为了阐明RNA修复的生物学意义，我们测试了这种修复是否可以挽救化学甲基化RNA的功能。我们证明，甲基化诱导的mRNA的翻译块可以很容易地缓解治疗与AlkB和hABH 3翻译前。此外，我们表明，化学甲基化的tRNA（苯丙氨酸）抑制氨酰化和翻译，但抑制可以逆转AlkB和hABH 3。在大肠杆菌中也观察到AlkB介导的tRNA 1-meA修复。coli中的表达。我们的数据表明，AlkB蛋白可以介导暴露于甲基化损伤的RNA的功能恢复，支持RNA修复是重要的这一观点。
Deleterious 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) lesions are introduced into nucleic acids by methylating agents. It was recently demonstrated that the E. coli AlkB protein and a human homolog, hABH3, can demethylate these lesions both in DNA and RNA. To elucidate the biological significance of the RNA repair, we have tested whether such repair can rescue the function of chemically methylated RNA. We demonstrate that a methylation-induced block in translation of an mRNA can be readily relieved by treatment with AlkB and hABH3 prior to translation. Furthermore, we show that chemical methylation of tRNA(Phe) inhibits aminoacylation and translation, but that the inhibition can be reversed by AlkB and hABH3. AlkB- mediated repair of 1-meA in tRNA was also observed in E. coli in vivo. Our data demonstrate that AlkB proteins can mediate functional recovery of RNA exposed to methylation damage, supporting the notion that RNA repair is important.