病毒是狡猾的小寄生虫：它们通过操纵被感染的细胞来繁殖，利用伪造命令制造新病毒。德国慕尼黑Ludwig Maximilian大学和Bonn大学科学家最近发现：细胞在命令中加入了“签名”抵御病毒。他们的结果发表在10月12号的《Science》上。
??每个细胞都能制造一系列蛋白质。指令来自于细胞核：这里是遗传物质DNA储存的地方。如果特定的蛋白质需要被制造，相应的指令会被复制，生成RNA分子，并通过核上小孔来到细胞质。然后在蛋白组装线上，核糖体严格按照RNA蓝图制成蛋白质。
??这一过程有个致命弱点：“敌人”能伪造命令，利用核糖体制造它们自己的蛋白质。例如病毒，这种由小蛋白外壳和中间的RNA分子构成的寄生生物。它们的RNA含有蛋白外壳序列。通过将RNA注入细胞，就能使外壳得到大量复制，进而得到更多病毒，攻击其它细胞。
??Bonn大学Gunther Hartmann教授说：“但是细胞有自己的抵抗方法，它们通常会发现外来RNA：制造干扰素，激发免疫细胞。它们还启动细胞凋亡。”
??目前细胞如何区分入侵者RNA还是未知数。但是小组结果表明：细胞核的指令带有一种签名，而病毒的没有。在病毒和细胞RNA链一端上都有三磷酸盐，但细胞RNA另一端还有一个分子帽。所有动植物RNA都有这个特征。
??但是有的RNA不含这一分子帽，它们能激发免疫反应或细胞凋亡。这有可能被用于病毒感染和癌症的治疗。
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.’
