病毒是狡猾的小寄生蟲：它們通過操縱被感染的細(xì)胞來繁殖，利用偽造命令制造新病毒。德國慕尼黑Ludwig  Maximilian大學(xué)和Bonn大學(xué)科學(xué)家最近發(fā)現(xiàn)：細(xì)胞在命令中加入了“簽名”抵御病毒,。他們的結(jié)果發(fā)表在10月12號的《Science》上,。

??每個細(xì)胞都能制造一系列蛋白質(zhì)。指令來自于細(xì)胞核：這里是遺傳物質(zhì)DNA儲存的地方。如果特定的蛋白質(zhì)需要被制造,，相應(yīng)的指令會被復(fù)制，生成RNA分子,，并通過核上小孔來到細(xì)胞質(zhì),。然后在蛋白組裝線上，核糖體嚴(yán)格按照RNA藍圖制成蛋白質(zhì),。

??這一過程有個致命弱點：“敵人”能偽造命令,，利用核糖體制造它們自己的蛋白質(zhì)。例如病毒,，這種由小蛋白外殼和中間的RNA分子構(gòu)成的寄生生物,。它們的RNA含有蛋白外殼序列。通過將RNA注入細(xì)胞,，就能使外殼得到大量復(fù)制,，進而得到更多病毒，攻擊其它細(xì)胞,。

??Bonn大學(xué)Gunther  Hartmann教授說：“但是細(xì)胞有自己的抵抗方法，它們通常會發(fā)現(xiàn)外來RNA：制造干擾素,，激發(fā)免疫細(xì)胞,。它們還啟動細(xì)胞凋亡。”

??目前細(xì)胞如何區(qū)分入侵者RNA還是未知數(shù),。但是小組結(jié)果表明：細(xì)胞核的指令帶有一種簽名,，而病毒的沒有。在病毒和細(xì)胞RNA鏈一端上都有三磷酸鹽,，但細(xì)胞RNA另一端還有一個分子帽,。所有動植物RNA都有這個特征。

??但是有的RNA不含這一分子帽,，它們能激發(fā)免疫反應(yīng)或細(xì)胞凋亡,。這有可能被用于病毒感染和癌癥的治療。

英文原文：

Molecular ’Signature’ Protects Cells from Viruses

Viruses are cunning little parasites: they breed by forcing the affected cells to do what they want. By fake commands they get them to produce new viruses. However, the cell often notices that there is something fishy going on. Researchers at the University of Bonn and Munich’s Ludwig Maximilian University have now discovered why: cells are in a position to attach their ‘signature’ to their commands, whereas viruses cannot. Their findings are published on 12 October in the prestigious journal Science.

Every cell constantly produces a whole arsenal of proteins. The instruction what is to be built comes from the cell nucleus: this is where the DNA is stored, the heredity molecule in which, so to speak, the construction blueprints for all cellular proteins are stored. If a particular protein is to be produced, the appropriate command is ‘copied’ in the cell nucleus. The copy consists of a DNA-like substance, the RNA. Via pores in the cell nucleus it reaches the cell plasma. The individual parts of the desired protein are put together there on a kind of assembly line. In this process the assembly line follows exactly the blueprint which is stored in the relevant RNA.

This method has an Achilles heel: ‘enemies’ can misuse the assembly line to produce their own proteins by faking the commands. Viruses, for example, basically consist of a small protein capsule which surrounds its genetic make-up – usually an RNA molecule. This RNA mainly contains the blueprint for new capsule proteins. By injecting its RNA into the cell, the virus re-programmes it: the cell production line then produces large numbers of new virus capsules. These are filled with virus RNA and attack more cells.

 ‘However, the cells are not completely at the mercy of a virus attack,’ Professor Gunther Hartmann, head of the Bonn University Clinic’s Department of Clinical Pharmacology. ‘They often recognise the alien RNA and set off the alarm: for example, they then produce what is known as the beta interferon, thereby activating specific killer cells. They also initiate the cell’s suicide programme – apoptosis. The viruses cannot then continue to breed.’

Up to now it was not known how cells distinguish their own RNA from that of the ‘enemy’. The latest findings, which a Japanese research team was also involved in, now shed light on the matter: they show that the instructions from the cell’s nucleus carry a kind of ‘signature’, which is missing in the virus commands. RNA is like a long string. In viruses there is a specific chemical signal, known as a triphosphate, located at one end of this string. The RNA in the cell’s nucleus basically also contains this triphosphate end. However, on top of it there is an additional short molecule, a molecular cap. ‘In all animals and plants the RNA which encodes proteins has this kind of molecular signature,’ Dr. Veit Hornung and Professor Stefan Endres of the Munich University Clinic’s Department of Clinical Pharmacology emphasise. ‘Apart from other functions it is also the signal that shows that the cell’s own RNA is involved.’

However, in all cells there are also RNAs which do not have a molecular cap. ‘Despite this they do not result in an immune reaction,’ Dr. Hornung says. ‘They sign their commands in a different way, viz. by means of a complex biochemical process which takes place in a special sub-structure of the cell’s nucleus, known as the nucleolus.’ These RNAs do not store information, being responsible for important tasks in ‘assembling’ the proteins.

Importance for therapy

The fact that RNAs without a ‘signature’ stimulate an immune reaction and initiate cell suicide opens up completely new perspectives for the therapy of virus infections and cancer cases: for example, RNA chains with a triphosphate end could be produced and fed into cancer cells. This could also trigger an anti-viral immune response. ‘Our findings are also important for gene therapy,’ Professor Hartmann stresses. ‘Before we attempt to cure diseases by introducing genetic material, we ought to understand precisely how the cells react to this genetic material.’