Transcription elongation factor S-II maintains transcriptional fidelity and confers oxidative stress resistance
Transcription elongation factor S-II maintains transcriptional fidelity and confers oxidative stress resistance
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DOI：
10.1046/j.1365-2443.2003.00677.x
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发表时间：
2003-10-01
期刊：
影响因子：
2.1
通讯作者：
Sekimizu, K
中科院分区：
文献类型：
--
作者：
Koyama, H;Ito, T;Sekimizu, K
背景资料：在转录延伸过程中，当不正确的核糖核苷酸被掺入新生的转录物中时，RNA聚合酶II在模板上被阻止。转录因子S-II增强RNA聚合酶II切除这些错误掺入的核苷酸，并刺激体外转录延伸。这种机制被认为是转录校对，但其生理相关性仍然unknow.Results：我们报告说，S-II有助于维持转录保真度在体内。我们采用了一种遗传报告基因测定法，利用突变的lacZ基因，当mRNA校对受损时，活性β-半乳糖苷酶蛋白表达。在S-II破坏突变酵母，β-半乳糖苷酶活性是野生型的9倍。S-II突变体表现出对氧化剂的敏感性，这是通过引入S-II基因抑制。突变体S-II蛋白，这是无法刺激转录的RNA聚合酶II在体外，没有抑制的突变体的敏感性，氧化应激或保持transformalfidelity.Conclusion：这些结果表明，S-II赋予氧化应激抗性，通过提供一个mRNA校对机制在转录延长。
Background: During transcription elongation, RNA polymerase II is arrested on the template when incorrect ribonucleotides are incorporated into the nascent transcripts. Transcription factor S-II enhances the excision of these mis-incorporated nucleotides by RNA polymerase II and stimulates transcription elongation in vitro. This mechanism is considered to be transcriptional proof-reading, but its physiological relevance remains unknown.Results: We report that S-II contributes to the maintenance of transcriptional fidelity in vivo. We employed a genetic reporter assay utilizing a mutated lacZ gene from which active beta-galactosidase protein is expressed when mRNA proof-reading is compromised. In S-II-disrupted mutant yeasts, beta-galactosidase activity was ninefold higher than that in wild-type. The S-II mutant exhibited sensitivity to oxidants, which was suppressed by introduction of the S-II gene. The mutant S-II proteins, which are unable to stimulate transcription by RNA polymerase II in vitro, did not suppress the sensitivity of the mutants to oxidative stress or maintain transcriptional fidelity.Conclusion: These results suggest that S-II confers oxidative stress resistance by providing an mRNA proof-reading mechanism during transcription elongation.