胚胎的細胞能夠以驚人的速度分化并形成完整的肌體,，但是細胞的這種生長和分裂是受控制的,，否則胚胎發(fā)育會發(fā)生障礙或者造成成年后癌癥的發(fā)生,。組織生長的控制是通過使一些細胞分化而另一些細胞死亡來實現(xiàn)的,，細胞的不同結(jié)局是由細胞內(nèi)分子信號決定的,。歐洲分子生物學(xué)實驗所的研究人員對果蠅細胞內(nèi)的一條信號通路是如何控制細胞的生存和死亡進行了研究,，研究結(jié)果將發(fā)表在本周的《細胞》學(xué)雜志上,。
??該課題的主要負責人之一Barry Thompson說：“Hippo信號通路能夠控制細胞的分裂與死亡，如果這條信號通路活性過高,，就會導(dǎo)致大量細胞分裂增殖而只有少量細胞死亡,，這樣組織就會增長過度，從而導(dǎo)致組織增生,。但是很久以來還沒有發(fā)現(xiàn)這個信號通路與細胞增殖的機制,。”
??利用先進的基因技術(shù)，Thompson和Cohen構(gòu)建了一種稱為bantam的microRNA小分子,，通過這個小分子他們將Hippo信號通路與細胞的增殖機制聯(lián)系在一起,。Bantam是一種參與細胞增殖的基因，沒有bantam的參與組織就會生長緩慢,，并且使組織比正常組織小,。而細胞產(chǎn)生bantam的量與Hippo信號通路的數(shù)量有關(guān)，更高水平的bantam會導(dǎo)致更多細胞的分裂,。
Thompson說：“bantam是一種罕見的RNA分子,，正常情況下RNA被用于制造蛋白質(zhì)，但是bantam不同,，它的作用是對RNA進行調(diào)節(jié),。當bantam與相應(yīng)的RNA結(jié)合后能夠阻斷被調(diào)節(jié)的RNA產(chǎn)生蛋白質(zhì)。從而降低細胞的分裂,。當bantam與RNA分離,，蛋白質(zhì)合成繼續(xù)。” Cohen的試驗室已經(jīng)對象bantam這樣的microRNA進行了長期的研究，因為這些microRNA在不同物種中許多重要過程中起著重要的調(diào)節(jié)作用,。下一步研究人員會尋找與bantam結(jié)合而起到調(diào)節(jié)作用的RNA,。這將有利于更好的了解Hippo信號通路，也許為該通路在組織生長,、人類腫瘤及其它生物中的作用提供啟示,。
英文原文：
A switch between life and death
Cells in an embryo divide at an amazing rate to build a whole body, but this growth needs to be controlled. Otherwise the result may be defects in embryonic development or cancer in adults. Controlling growth requires that some cells divide while others die; their fates are determined by signals that are passed from molecule to molecule within the cell. Researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg have now discovered how one of these signaling pathways controls the life and death of cells in the fruit fly.
The breakthrough came as Barry Thompson from Stephen Cohen’s group at EMBL looked at a recently discovered signaling pathway called “Hippo”.
“Hippo acts as a switch between cell division and death,” says Barry Thompson, “If the pathway is too active, tissues overgrow because too many cells divide and too few die. But until now, we hadn’t found a connection between the signals and the cellular machinery that drives growth.”
Using sophisticated genetic techniques, Thompson and Cohen established that a small molecule, a microRNA called bantam, makes this link. Without bantam, tissues grow too slowly and remain smaller than normal. The amount of bantam produced by the cell directly depends on the amount of traffic on the Hippo signaling pathway, and higher levels of bantam prompt more cell division.
“Bantam is an unusual type of RNA molecule,” Thompson says. “Normally, RNAs go on to make protein, but bantam is different. Its job is to regulate other RNAs by attaching itself to them; the result is that they block their expression into proteins. In this case, those proteins would go on to shut down cell division. With bantam around, the brake is off, and they continue to divide.”
Cohen and his lab have been studying microRNAs like bantam for some time because of their important role in the regulation of many vital processes across species. The next step will be to identify the RNAs that bantam docks onto to control. This will provide a more complete view of the Hippo pathway and may provide insights into the central role it plays in tissue growth and cancers in humans and other organisms.
