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【bio-news】人造RNA可区分核糖体功能的开与关
Artificial RNA ligands differentiate between on and off states of riboswitches
Contact: Michael Famulok, Universität Bonn (Germany)
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RNA Ligands That Distinguish Metabolite-Induced Conformations in the TPP Riboswitch
How does an organism know when it must produce a protein and in what amount? Clever control mechanisms are responsible for the regulation of protein biosynthesis. One such type of mechanism, discovered only a few years ago, is riboswitches, which function as a sort of “off” switch for the production of certain proteins. These could be a useful point of attack for novel antibiotics if it were possible to find drugs that bind to the switches of pathogens and “turn off” the biosynthesis of essential proteins in bacteria or fungi. A team at the interdisciplinary Life and Medical Sciences Center at the University of Bonn has now taken a meaningful step toward a better understanding of riboswitches. Researchers led by Michael Famulok have successfully produced hairpin-shaped RNA molecules that are able to differentiate between riboswitches in the on and off states.
In order to produce a specific protein, a cell first generates a copy of the corresponding gene of the DNA. This blueprint containing the construction plans for the protein is called messenger RNA (mRNA). By using its ribosomes, the cell then reads the mRNA code and synthesizes the protein. Some proteins can activate a “switch” to halt their own synthesis once they are present in sufficient quantity. This is because the mRNA does not only contain the genetic code for the protein but can also contain segments with a switching function. The protein or a closely connected metabolite binds to this riboswitch and changes its spatial structure such that the mRNA segments controlling the protein production can no longer be read off. For example, when the metabolite thiamine pyrophosphate (TPP) binds to the thiM riboswitch of E. coli bacteria, an mRNA segment recognized by the ribosome as the starting point for “reading” the plan is covered up.
Michael Famulok and his team searched for a probe that can differentiate between off and on. Aptamers are known for their ability to differentiate between different states of proteins. Aptamers are short RNA strands that adopt a specific spatial structure and, like antibodies, selectively bind to specific target molecules. So, why not riboswitches? Over several steps starting from a “library”, a randomly generated large number of highly varied RNA sequences, the scientists selected two short hairpin-shaped aptamers that bind very strongly and specifically to the riboswitch in the “on” position. It turned out that the two hairpins bind to different locations: one to the TPP binding site and the other to a domain responsible for the change in structure of the riboswitch. Both hairpins are crowded when TPP molecules move the riboswitch to the “off” conformation.
Famulok and his team hope to use these aptamers to gain new insights into the function of riboswitches. This could help in the search for a completely new class of antimicrobial agents that block the bacterial thiM riboswitch just like TPP. http://www.cutech.edu.cn/ShowArticle.asp?ArticleID=19236
这条新闻已被翻译，但我觉得内容欠妥，所以自己翻译了一下。最近比较忙，很久没翻译了， 请逃主任见谅。
人造RNA可区分核糖体功能的开与关
RNA适体可区分焦磷酸硫胺素（TPP）诱导的核糖体构型转换
生物体的蛋白合成由精细机制调控。传统机制是细胞内核糖体具有开关状态，开启即合成相应蛋白。细菌和真菌核糖体是药物的有效靶点，可寻找新的抗生素作用核糖体，阻止病原蛋白的合成。德国波恩大学的研究小组成功地发现了一种发夹RNA分子，它可区分核糖体的开与关。
细胞合成蛋白之前，首先需要相应信使RNA（mRNA）。mRNA包含相应蛋白氨基酸残基密码子，核糖体可阅读mRNA密码子，合成蛋白。某些蛋白的合成量足够时，可关闭核糖体，阻止其自身合成。因为mRNA不仅包含相应蛋白的基因密码，而且包含控制核糖体开关的信息。蛋白本身或相关代谢物可同核糖体结合，改变其空间结构，从而抑制蛋白合成。比如焦磷酸硫胺素（TPP）可同大肠杆菌核糖体结合，遮盖核糖体mRNA读码框的起始位点，阻止蛋白合成。
众所周知，适配体可区分蛋白的不同状态。适配体是短链RNA，具有特异空间结构，像抗体一样同靶分子特异结合。Michael团队试图寻找一种适配体，以区分核糖体的开和关。他们从随机生成的RNA文库中筛选出两个短发夹RNA，可同开启状态的核糖体特异结合。这两个适配体定位不同，一个结合TPP结合位点，另一个结合核糖体结构变化决定域。当TPP促使核糖体关闭后，这两个发夹均失去结合活力。
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作者:admin@医学,生命科学 2011-04-07 17:17
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