Based on the stereotypical hairpin structure, researchers scanned genomes and found more than 38,000 likely precursors; Nearly 50,000 mature microRNAs have been discovered by sequencing all RNA found in cells from a variety of species. Although common in animals, they have also been discovered in plants, raising the possibility that they existed in a single-celled ancestral organism.
While some microRNA genes, including lin-4 And late-7have dramatic phenotypes when mutated; many have weak or confusing effects. This is likely in part due to the fact that a single microRNA can bind to and regulate a variety of genes, and thus can have a mix of effects when mutated. In other cases, different microRNAs may bind to the same messenger RNA, creating a redundancy that makes the loss of a single microRNA difficult to detect.
Nevertheless, there is ample evidence that together they are essential for the normal development of many organisms and tissues. Knocking out the gene encoding the Dicer protein, which is required for the formation of mature microRNAs, causes early embryonic lethality. Silencing the gene in specific cell types causes a variety of defects. For example, B cells never mature if Dicer is lost in that cell lineage, and a knockout in nerve cells causes microcephaly and limited branching of connections between neurons, causing the animals to die shortly after birth.
Because it concerns the Medicine Prize, the Nobel Committee also mentions a number of human genetic diseases that are caused by mutations in microRNA genes.
Overall, the award highlights how complex life is at the cellular level. There are quite a number of genes that must be made by each cell simply in order to survive. But as for the rest, they are embedded in complex regulatory networks that work together to ensure that proteins are made only where and when they are needed, and are often broken down if they are somehow made. And every now and then, basic research in a strange species still tells us unexpected things about those networks.
