瑞士實驗性癌癥研究所與帕維亞大學合作研究發(fā)現(xiàn),，端粒也有RNA。端粒位于染色體末端,，每次細胞分裂時它都會逐漸縮短,。
據(jù)每日科學報道，發(fā)表在《科學快遞》上的這項研究使我們對以前所了解的端粒功能產(chǎn)生了懷疑,，有可能為停止癌細胞端粒更新提供新的手段,。
在細胞核內，我們所有的遺傳信息都包含在染色體里呈螺旋狀的雙股DNA分子中,。在這些染色體的末端就是端粒,，是DNA鏈復制帶，就像鞋帶的塑料頂端,，保護線粒體不被磨損，以及細胞分裂時遺傳信息不至于混淆,。
端粒就像是細胞的時鐘,，因為在每次細胞分裂時它都首先要縮短。當細胞生長并經(jīng)歷幾次分裂后，端粒就會開啟警報系統(tǒng)防止細胞進一步分裂,。如果這個時鐘不能正常工作,，細胞就會因線粒體損害而告終或者進行無休止的分裂，從而引起癌癥或疾病,。了解端粒的功能和如何控制這一功能至關重要,。
染色體內的DNA的作用就像細胞的一個工藝流程。遺傳信息轉錄到RNA片斷,，它再在細胞內發(fā)揮各種作用,，如制造蛋白、催化化學反應或者維持細胞構造,。一般認為,，如果端粒是靜止的，DNA上的信息就不能轉錄給RNA,。研究人員發(fā)現(xiàn)端粒RNA并證明RNA是從端粒DNA轉錄來的,。
在胚胎細胞（還有一些干細胞），一種叫做端粒末端轉移酶的酶可以重建端粒,，以便細胞能保持分裂,。隨著時間延長，端粒末端酶會減少,，最終端粒也會縮短,，細胞就不能繼續(xù)分裂。而在癌癥細胞里,，端粒末端酶重建端粒的時間超過了細胞的正常壽命,，細胞就會無休止地分裂而形成腫瘤。研究人員估計,，90%的癌癥中端粒一直處于活躍狀態(tài),。但端粒維持活躍狀態(tài)的機制一直還不清楚。研究人員發(fā)現(xiàn),，端粒中的RNA受端粒末端酶中的一種蛋白調節(jié),，這一發(fā)現(xiàn)揭開了端粒功能的關鍵問題。
"要給出能否會導致癌癥治療的最后答案還為時過早,。"文章作者約阿希姆.琳納爾說,，"但實驗證明，端粒RNA為攻擊癌癥細胞中端粒以便使其停止生長提供了新的靶點,。"
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)
