Introduction to microRNA

How many genes do humans have compared to rice or C. elegans? What is meant by “junk DNA”, or “dark matter of human genome”? How can we use microRNA to control gene expression? Associate Professor of Neurology and Neurobiology at Harvard Medical School and the Principal Investigator of Krichevsky Lab at Brigham and Women’s Hospital Anna M. Krichevsky speaks on the discovery of microRNA, and its further use in different areas of research.

The discovery of these molecules really has been of the major discoveries in molecular biology over last, maybe, 20 years. Our genome is very interesting. Apparently, the size of a genome really does not correlate very with the organism’s complexity. What I mean here: if you take a fly, or a worm, or plants, or humans, the genome size really does not tell you much about the complexity of the organism. Furthermore, the number of genes in the genome really does not correlate with the organism complexity. To give you an example: the number of genes in Drosophila, a fly, is very close to the number of genes in the human genome.

MicroRNAs have been discovered only recently. In fact, as a class, they have been discovered in 2001. There are many of them: in human genome, I believe, there are approximately 2000 of microRNA genes discovered. They are expressed pretty much in all multicellular organisms, and in some unicellular organisms as well. There are some microRNAs that are species-specific, others are evolutionarily very well conserved. It means, in Drosophila brain you will find the same molecules that are expressed in human brains. Some of them are very tissue-specific, which means, you can say, that this miR-X, if you see this miR-X, it means, that you’re dealing with, for example, a muscle cell; if you see miR-B, it means, that you’re looking at a liver cell.

MicroRNA regulate gene expression post-transcriptionally, which means that they regulate expression of mRNA to the protein. Practically, they bind to a messenger RNA, usually within its untranslated regions, usually within a 3′ untranslated region and it’s a regulatory region, and they prevent their translation to a protein, so usually they are repressors of gene expression. They can also destabilize the message. There are several modes of action, but the outcome is that message is not producing a protein or producing less of the protein.