The function of the imprinted microRNA-483 in growth, metabolism and cancer

microrna是一种小分子，它控制着身体产生蛋白质的数量，以及这些蛋白质产生的时间。由于这种作用，它们对生物体的发育和健康非常重要。许多microrna的精确功能，估计在人类中有数百种，是未知的。这些小分子中的许多都是由基因内部产生的，它们依赖于这些基因的产生机制。MiR-483是一种microRNA，由体内一种叫做Igf2的重要生长因子的产生机制产生。我们知道Igf2的作用，它促进生长，也与我们能储存多少脂肪和糖有关，但对它的伙伴microRNA却一无所知。我们做了一个有趣的观察：当我们制造一只没有microRNA的老鼠，但仍能正常分泌生长因子Igf2时，这导致了出生后的过度生长（基因工程的老鼠比没有基因工程的兄弟姐妹重10%左右）。这一令人兴奋的结果表明，这种microRNA的主要功能是抑制生长，其功能与宿主基因恰恰相反！我们现在想了解更多关于这个microRNA的信息——除了调节出生后的生长，它还有什么作用？它是否参与了我们控制脂肪和糖储存的多种方式，以及我们如何利用这些储存？它在癌症等生长疾病中起作用吗？这个microRNA帮助控制哪些基因和蛋白质？我们能精确地找到它是如何工作的吗？这个项目很重要，因为它可以为我们提供关于microRNA如何工作的新线索，特别是在生长控制方面（据我们所知，这是microRNA参与控制体型的第一个例子）。如果事实证明它的正常功能确实是抑制生长，那么考虑使用它作为抗癌疗法将是非常重要的。其他生长控制疾病，如那些导致小婴儿和大婴儿的疾病，有或没有产后生长补偿，也可能从我们的研究中受益。

MicroRNAs are small molecules that control the amount of proteins that the body makes, as well as the timing that these proteins are made. Because of this action they are very important for development and the health of organisms. The precise function of many microRNAs, estimated to be in their hundreds in humans, is unknown. Many of these small molecules are made from inside genes and they are dependent on those genes machinery to be produced. MiR-483 is a microRNA that is produced by the machinery that makes an important growth factor in the body called Igf2. We know what Igf2 does, it promotes growth and is also involved in how much fat and sugar we can store, but nothing is known about its partner microRNA. We have made an interesting observation: when we make a mouse that does not have the microRNA, but still makes the growth factor Igf2 normally, this results in postnatal overgrowth (the genetically engineered mice are about 10% heavier than their brothers and sisters that were not engineered). This exciting results suggests that the main function of this microRNA is to put the brakes on growth, a function that is precisely the opposite of its host gene! We now want to find out more about this microRNA - what else does it do in addition to regulate postnatal growth? Is it involved in the many ways we control fat and sugar storage and how we use those stores? Does it have a role in diseases of growth such as cancer? What genes and proteins does this microRNA help to control? Can we find precisely how it works? This project is important because it can give us new clues on how microRNAs work, in particular in growth control (as far as we know this is the first example of an microRNA involved in control of body size). If it turns out that its normal function is indeed to put down the brakes on growth it will be very important to consider using it as an anti-cancer therapy. Other diseases of growth control, such as those that lead to smaller babies and big babies, with and without postnatal growth compensation may also benefit from our research.