Science：古老蛋白质助细菌清除垃圾基因
专题：Science报道
生物谷报道：美国纽约大学医学院的科学家在5月16日《科学》发表论文，表示在细菌基因组内发现了一种名为Rho的蛋白质，它具有调节功能，能够平衡基因的活性并能结合辅助因子“沉默”外来DNA。因为这种蛋白质的存在而使原核生物基因组中几乎不存在“垃圾基因”。
“垃圾基因”是指不编码RNA或蛋白质的基因序列。真核生物的基因组中含有大量的不编码序列，然而细菌基因组却罕见这种现象。
研究小组结合基因组学和蛋白质组学方法，用双环霉素抑制Rho的活性，观测了基因的开关情况。接下来，研究人员利用微分基因电泳（DIGE）技术挑出了大肠杆菌基因响应抗生素而产生的蛋白，并用质谱学方法鉴别了这些蛋白。结果表明Rho是广泛存在的，它几乎能够终止所有基因内的转录。它的第一个主要功能就是调节转录水平以适应细菌的翻译需求，也就是说Rho确保细菌不会负荷太多的蛋白，Rho对于细菌的生存是必需的，因为它似乎沉默了潜在的有毒基因。Rho是一种古老的蛋白，细菌中到处都是，研究人员推测Rho使细菌能够快速生长。在进化过程中，Rho可能使得基因被紧凑地‘打包’起来，从而反过来促进了细菌的快速生长。
另外，通过进一步分析，研究人员发现，Rho能够连同两个辅助因子一起“沉默”大肠杆菌体内的外来DNA。此外来DNA对大肠杆菌细胞具有毒性，在数百万年前通过基因横向转移进入大肠杆菌体内。
研究人员表示，这一发现可能有助于开发其它标靶Rho的抗生素，因为大多数细菌对抗生素的抗性都是通过横向转移获得的。（生物谷www.bioon.com）
生物谷推荐原始出处：
Science，Vol. 320. no. 5878, pp. 935 – 938，Christopher J. Cardinale，Evgeny Nudler
Termination Factor Rho and Its Cofactors NusA and NusG Silence Foreign DNA in E. coli
Transcription of the bacterial genome by the RNA polymerase must terminate at specific points. Transcription can be terminated by Rho factor, an essential protein in enterobacteria. We used the antibiotic bicyclomycin, which inhibits Rho, to assess its role on a genome-wide scale. Rho is revealed as a global regulator of gene expression that matches Escherichia coli transcription to translational needs. We also found that genes in E. coli that are most repressed by Rho are prophages and other horizontally acquired portions of the genome. Elimination of these foreign DNA elements increases resistance to bicyclomycin. Although rho remains essential, such reduced-genome bacteria no longer require Rho cofactors NusA and NusG. Deletion of the cryptic rac prophage in wild-type E. coli increases bicyclomycin resistance and permits deletion of nusG. Thus, Rho termination, supported by NusA and NusG, is required to suppress the toxic activity of foreign genes.
1 Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
2 Department of Microbiology, Columbia University Medical Center, New York, NY 10032, USA.
3 BioMaPS Institute for Quantitative Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
4 Comparative Proteomics Center, Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
5 Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
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