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【科普】细胞分泌特殊蛋白质应对“生命威胁”
在12月16日的《PLoS遗传学》（PLoS Genetics）上，研究人员报告，当面临压力时，细胞会重组一个复杂的RNA分子化学修饰系统。
实验中，研究人员使用4种有毒化学物质（MMS、过氧化氢、砷、漂白剂）处理酵母细胞。借助多元统计分析，研究人员鉴别出了细胞针对不同化学物质展现的不同反应。随后，当敲除某特定蛋白质（其对RNA修复具有重要作用）后，细胞变得更易受有毒化学物质的伤害。
论文通讯作者之一、MIT生物工程学教授彼得?德登（Peter Dedon）说，细胞的这一反应机制可能对压力刺激和荷尔蒙均适用。Dedon目前正在研究细菌如何利用这一机制响应人体白细胞的攻击，或能帮助研究人员开发新的抗生素来对抗这一防御系统。（科学网 梅进/编译） http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1001247
Abstract Top
Decades of study have revealed more than 100 ribonucleoside structures incorporated as post-transcriptional modifications mainly in tRNA and rRNA, yet the larger functional dynamics of this conserved system are unclear. To this end, we developed a highly precise mass spectrometric method to quantify tRNA modifications in Saccharomyces cerevisiae. Our approach revealed several novel biosynthetic pathways for RNA modifications and led to the discovery of signature changes in the spectrum of tRNA modifications in the damage response to mechanistically different toxicants. This is illustrated with the RNA modifications Cm, m5C, and m22G, which increase following hydrogen peroxide exposure but decrease or are unaffected by exposure to methylmethane sulfonate, arsenite, and hypochlorite. Cytotoxic hypersensitivity to hydrogen peroxide is conferred by loss of enzymes catalyzing the formation of Cm, m5C, and m22G, which demonstrates that tRNA modifications are critical features of the cellular stress response. The results of our study support a general model of dynamic control of tRNA modifications in cellular response pathways and add to the growing repertoire of mechanisms controlling translational responses in cells.
Author Summary Top
While the genetic code in DNA is read from four nucleobase structures, there are more than 100 ribonucleoside structures incorporated as post-transcriptional modifications mainly in tRNA and rRNA. These structures and their biosynthetic machinery are highly conserved, with 20–30 present in any one organism, yet the larger biological function of the modifications has eluded understanding. To this end, we developed a sensitive and precise mass spectrometric method to quantify 23 of the 25 ribonucleosides in the model eukaryotic yeast, Saccharomyces cerevisiae. We discovered that the spectrum of ribonucleosides shifts predictably when the cells are exposed to different toxic chemical stimulants, with these signature changes in the spectrum serving as part of the cellular survival response to these exposures. The method also revealed novel enzymatic pathways for the synthesis of several modified ribonucleosides. These results suggest a dynamic reprogramming of the tRNA and rRNA modifications during cellular responses to stimuli, with corresponding modifications working as part of a larger mechanism of translational control during the cellular stress response. [标签:content2]
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作者:admin@医学,生命科学 2011-01-26 23:22
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