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首页> 外文期刊>Molecular and Cellular Biology >Elongator Protein 3b Negatively Regulates Ribosomal DNA Transcription in African Trypanosomes
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Elongator Protein 3b Negatively Regulates Ribosomal DNA Transcription in African Trypanosomes

机译：延伸蛋白3b负调节非洲锥虫的核糖体DNA转录。

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Eukaryotic cells limit ribosomal DNA (rDNA) transcription by RNA polymerase I (RNAP-I) to maintain genome integrity. African trypanosomes present an excellent model for studies on RNAP-I regulation because they possess a bifunctional RNAP-I and because RNAP-II transcription appears unregulated. Since Elp3, the catalytic component of Elongator, controls RNAP-II transcription in yeast and human cells, we predicted a role for a trypanosome Elp3-related protein, ELP3a or ELP3b, in RNAP-I regulation. elp3b null and conditional strains specifically exhibited resistance to a transcription elongation inhibitor, suggesting that ELP3b negatively impacts elongation. Nascent RNA analysis and expression of integrated reporter cassettes supported this interpretation and revealed negative control of rDNA transcription. ELP3b specifically localized to the nucleolus, and ELP3b loss rendered cells hypersensitive to DNA damage and to translation inhibition, suggesting that anti-Elongator function was important to maintain genome integrity rather than to modulate ribosome production. Finally, ELP3b displayed discrimination between RNAP-I compartments in the same cell. Our results establish ELP3b as a major negative regulator of rDNA transcription and extend the roles of the Elp3-related proteins to RNAP-I transcription units. ELP3b is also the first trypanosome protein shown to distinguish between rDNA and variant surface glycoprotein transcription within different RNAP-I compartments.
机译：真核细胞通过RNA聚合酶I（RNAP-1）限制核糖体DNA（rDNA）转录，以维持基因组完整性。非洲锥虫为RNAP-I调控研究提供了一个极好的模型，因为它们具有双功能RNAP-I，并且RNAP-II转录似乎不受调控。由于Elp3是Elongator的催化成分，它控制酵母和人类细胞中的RNAP-II转录，因此我们预测了锥虫Elp3相关蛋白ELP3a或ELP3b在RNAP-1调控中的作用。 elp3b 空菌株和条件菌株对转录延伸抑制剂表现出特殊的抗性，这表明ELP3b对延伸产生负面影响。新生RNA分析和整合的报告盒的表达支持这种解释，并揭示了rDNA转录的负控制。 ELP3b特异地定位在核仁上，而ELP3b的缺失使细胞对DNA损伤和翻译抑制高度敏感，这表明抗延伸剂功能对于维持基因组完整性而不是调节核糖体的产生很重要。最后，ELP3b在同一细胞中的RNAP-1区室之间显示出区别。我们的研究结果将ELP3b确立为rDNA转录的主要负调节剂，并将Elp3相关蛋白的作用扩展到RNAP-1转录单位。 ELP3b也是第一个锥虫蛋白，显示出可以区分rRNA和不同RNAP-I区室中的变异表面糖蛋白转录。

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