瑞士实验性癌症研究所与帕维亚大学合作研究发现，端粒也有RNA。端粒位于染色体末端，每次细胞分裂时它都会逐渐缩短。
据每日科学报道，发表在《科学快递》上的这项研究使我们对以前所了解的端粒功能产生了怀疑，有可能为停止癌细胞端粒更新提供新的手段。
在细胞核内，我们所有的遗传信息都包含在染色体里呈螺旋状的双股DNA分子中。在这些染色体的末端就是端粒，是DNA链复制带，就像鞋带的塑料顶端，保护线粒体不被磨损，以及细胞分裂时遗传信息不至于混淆。
端粒就像是细胞的时钟，因为在每次细胞分裂时它都首先要缩短。当细胞生长并经历几次分裂后，端粒就会开启警报系统防止细胞进一步分裂。如果这个时钟不能正常工作，细胞就会因线粒体损害而告终或者进行无休止的分裂，从而引起癌症或疾病。了解端粒的功能和如何控制这一功能至关重要。
染色体内的DNA的作用就像细胞的一个工艺流程。遗传信息转录到RNA片断，它再在细胞内发挥各种作用，如制造蛋白、催化化学反应或者维持细胞构造。一般认为，如果端粒是静止的，DNA上的信息就不能转录给RNA。研究人员发现端粒RNA并证明RNA是从端粒DNA转录来的。
在胚胎细胞（还有一些干细胞），一种叫做端粒末端转移酶的酶可以重建端粒，以便细胞能保持分裂。随着时间延长，端粒末端酶会减少，最终端粒也会缩短，细胞就不能继续分裂。而在癌症细胞里，端粒末端酶重建端粒的时间超过了细胞的正常寿命，细胞就会无休止地分裂而形成肿瘤。研究人员估计，90%的癌症中端粒一直处于活跃状态。但端粒维持活跃状态的机制一直还不清楚。研究人员发现，端粒中的RNA受端粒末端酶中的一种蛋白调节，这一发现揭开了端粒功能的关键问题。
"要给出能否会导致癌症治疗的最后答案还为时过早。"文章作者约阿希姆.琳纳尔说，"但实验证明，端粒RNA为攻击癌症细胞中端粒以便使其停止生长提供了新的靶点。"
英文原文：
New Telomere Discovery Could Help Explain Why Cancer Cells Never Stop Dividing
Science Daily
Date: October 7, 2007
Science Daily — A group working at the Swiss Institute for Experimental Cancer Research (ISREC) in collaboration with the University of Pavia has discovered that telomeres, the repeated DNA-protein complexes at the end of chromosomes that progressively shorten every time a cell divides, also contain RNA. A human metaphase stained for telomeric repeats. DAPI stained chromosomes are false-colored in red, telomeres are in green. (Credit: Claus Azzalin, ISREC)
This discovery, published in Science Express, calls into question our understanding of how telomeres function, and may provide a new avenue of attack for stopping telomere renewal in cancer cells.
Inside the cell nucleus, all our genetic information is located on twisted, double stranded molecules of DNA which are packaged into chromosomes. At the end of these chromosomes are telomeres, zones of repeated chains of DNA that are often compared to the plastic tips on shoelaces because they prevent chromosomes from fraying, and thus genetic information from getting scrambled when cells divide.
The telomere is like a cellular clock, because every time a cell divides, the telomere shortens. After a cell has grown and divided a few dozen times, the telomeres turn on an alarm system that prevents further division. If this clock doesn't function right, cells either end up with damaged chromosomes or they become "immortal" and continue dividing endlessly -- either way it's bad news and leads to cancer or disease. Understanding how telomeres function, and how this function can potentially be manipulated, is thus extremely important.
The DNA in the chromosome acts like a sort of instruction manual for the cell. Genetic information is transcribed into segments of RNA that then go out into the cell and carry out a variety of tasks such as making proteins, catalyzing chemical reactions, or fulfilling structural roles. It was thought that telomeres were "silent" -- that their DNA was not transcribed into strands of RNA. The researchers have turned this theory on its head by discovering telomeric RNA and showing that this RNA is transcribed from DNA on the telomere.
A human metaphase stained for telomeric repeats. DAPI stained chromosomes are false-colored in red, telomeres are in green. (Credit: Claus Azzalin, ISREC)
Why is this important" In embryonic cells (and some stem cells), an enzyme called telomerase rebuilds the telomere so that the cells can keep dividing. Over time, this telomerase dwindles and eventually the telomere shortens and the cell becomes inactive. In cancer cells, the telomerase enzyme keeps rebuilding telomeres long past the cell's normal lifetime. The cells become "immortal", endlessly dividing, resulting in a tumor. Researchers estimate that telomere maintenance activity occurs in about 90% of human cancers. But the mechanism by which this maintenance takes place is not well understood. The researchers discovered that the RNA in the telomere is regulated by a protein in the telomerase enzyme. Their discovery may thus uncover key elements of telomere function.
"It's too early to give yet a definitive answer," to whether this could lead to new cancer therapies, notes Joachim Lingner, senior author on the paper. "But the experiments published in the paper suggest that telomeric RNA may provide a new target to attack telomere function in cancer cells to stop their growth."
Joachim Lingner is an Associate Professor at the EPFL (Ecole Polytechnique Fédérale de Lausanne). Funding for this research was provided in part by the Swiss National Science Foundation NCCR "Frontiers in Genetics".
Article: "Telomeric Repeat Containing RNA and RNA Surveillance Factors at Mammalian Chromosome Ends"
Note: This story has been adapted from material provided by Ecole Polytechnique Fédérale de Lausanne.
A human metaphase stained for telomeric repeats. DAPI stained chromosomes are false-colored in red, telomeres are in green. (Credit: Claus Azzalin, ISREC)
