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

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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.