生物谷報(bào)道:美國紐約大學(xué)醫(yī)學(xué)院的科學(xué)家在5月16日《科學(xué)》發(fā)表論文,,表示在細(xì)菌基因組內(nèi)發(fā)現(xiàn)了一種名為Rho的蛋白質(zhì),,它具有調(diào)節(jié)功能,能夠平衡基因的活性并能結(jié)合輔助因子“沉默”外來DNA,。因?yàn)檫@種蛋白質(zhì)的存在而使原核生物基因組中幾乎不存在“垃圾基因”,。
“垃圾基因”是指不編碼RNA或蛋白質(zhì)的基因序列。真核生物的基因組中含有大量的不編碼序列,,然而細(xì)菌基因組卻罕見這種現(xiàn)象,。
研究小組結(jié)合基因組學(xué)和蛋白質(zhì)組學(xué)方法,用雙環(huán)霉素抑制Rho的活性,,觀測(cè)了基因的開關(guān)情況,。接下來,研究人員利用微分基因電泳(DIGE)技術(shù)挑出了大腸桿菌基因響應(yīng)抗生素而產(chǎn)生的蛋白,,并用質(zhì)譜學(xué)方法鑒別了這些蛋白,。結(jié)果表明Rho是廣泛存在的,它幾乎能夠終止所有基因內(nèi)的轉(zhuǎn)錄,。它的第一個(gè)主要功能就是調(diào)節(jié)轉(zhuǎn)錄水平以適應(yīng)細(xì)菌的翻譯需求,,也就是說Rho確保細(xì)菌不會(huì)負(fù)荷太多的蛋白,Rho對(duì)于細(xì)菌的生存是必需的,,因?yàn)樗坪醭聊藵撛诘挠卸净?。Rho是一種古老的蛋白,細(xì)菌中到處都是,,研究人員推測(cè)Rho使細(xì)菌能夠快速生長,。在進(jìn)化過程中,Rho可能使得基因被緊湊地‘打包’起來,,從而反過來促進(jìn)了細(xì)菌的快速生長,。
另外,,通過進(jìn)一步分析,研究人員發(fā)現(xiàn),,Rho能夠連同兩個(gè)輔助因子一起“沉默”大腸桿菌體內(nèi)的外來DNA,。此外來DNA對(duì)大腸桿菌細(xì)胞具有毒性,在數(shù)百萬年前通過基因橫向轉(zhuǎn)移進(jìn)入大腸桿菌體內(nèi),。
研究人員表示,,這一發(fā)現(xiàn)可能有助于開發(fā)其它標(biāo)靶Rho的抗生素,因?yàn)榇蠖鄶?shù)細(xì)菌對(duì)抗生素的抗性都是通過橫向轉(zhuǎn)移獲得的,。(生物谷www.bioon.com)
生物谷推薦原始出處:
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
Christopher J. Cardinale,1* Robert S. Washburn,2* Vasisht R. Tadigotla,3 Lewis M. Brown,4 Max E. Gottesman,2,5 Evgeny Nudler1
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.