胚胎的细胞能够以惊人的速度分化并形成完整的肌体，但是细胞的这种生长和分裂是受控制的，否则胚胎发育会发生障碍或者造成成年后癌症的发生。组织生长的控制是通过使一些细胞分化而另一些细胞死亡来实现的，细胞的不同结局是由细胞内分子信号决定的。欧洲分子生物学实验所的研究人员对果蝇细胞内的一条信号通路是如何控制细胞的生存和死亡进行了研究，研究结果将发表在本周的《细胞》学杂志上。
??该课题的主要负责人之一Barry Thompson说：“Hippo信号通路能够控制细胞的分裂与死亡，如果这条信号通路活性过高，就会导致大量细胞分裂增殖而只有少量细胞死亡，这样组织就会增长过度，从而导致组织增生。但是很久以来还没有发现这个信号通路与细胞增殖的机制。”
??利用先进的基因技术，Thompson和Cohen构建了一种称为bantam的microRNA小分子，通过这个小分子他们将Hippo信号通路与细胞的增殖机制联系在一起。Bantam是一种参与细胞增殖的基因，没有bantam的参与组织就会生长缓慢，并且使组织比正常组织小。而细胞产生bantam的量与Hippo信号通路的数量有关，更高水平的bantam会导致更多细胞的分裂。
Thompson说：“bantam是一种罕见的RNA分子，正常情况下RNA被用于制造蛋白质，但是bantam不同，它的作用是对RNA进行调节。当bantam与相应的RNA结合后能够阻断被调节的RNA产生蛋白质。从而降低细胞的分裂。当bantam与RNA分离，蛋白质合成继续。” Cohen的试验室已经对象bantam这样的microRNA进行了长期的研究，因为这些microRNA在不同物种中许多重要过程中起着重要的调节作用。下一步研究人员会寻找与bantam结合而起到调节作用的RNA。这将有利于更好的了解Hippo信号通路，也许为该通路在组织生长、人类肿瘤及其它生物中的作用提供启示。
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.
