Therapy Analysis - microRNA
Micro-Management
How microRNA could revolutionize traditional thinking on targeted drug development
The discovery of microRNA
Perhaps this is a time for turning old ideas on their heads. Novelty may create value, but has been slow to create blockbusters. An accidental discovery can bypass years of painstaking research. And DNA may make RNA (sometimes) - but RNA can do a great many other things besides making protein. The Human Genome Project yielded data on hundreds of hitherto unknown proteins, ripe for investigation as therapeutic targets - but this was not the end of the story. Hidden among the previously-unfashionable realm of 'noncoding' sequences lay what may emerge as the real master-regulators of biological systems, opening up a whole new area for pharmaceutical R&D, and one which seriously challenges our preconceptions regarding specificity of drug targeting.
MicroRNA (also known as miRNA), once disregarded simply as a part of 'junk' RNA, was first encountered in 1993 by Victor Ambros and his colleagues Rosalind Lee and Rhonda Feinbaum at Harvard University, while studying developmental mutants of the nematode Caenorhabditis elegans. When homing in on a putative 'protein', lin-4, a sequence regulating heterochronic temporal control of development, the research team was surprised to find that lin-4 was no protein, but actually a short hairpin RNA with powerful regulatory functions.
As with many seminal discoveries of this sort, the wider implications did not become immediately apparent. It was not until 2001 that short RNA sequences of the type discovered by Ambros's team were found to be widely distributed in many species, including Drosophila and humans, following extensive studies in Ambros's own group and the laboratories of David Bartel and Thomas Tuschl at the MIT, and the term 'microRNA' was coined. At that point it became apparent that these sequences, only 17-24 nucleotides long, were highly conserved, and had profound and complex regulatory functions in their host organisms. In 2005, it was conservatively estimated that miRNAs could influence the expression of 30% of all human genes, and latest calculations have predicted the presence of some 1,000 human miRNAs, around 500 of which have already been isolated, and a few have been characterized in considerable detail. These sequences are produced within the cell by transcription from individual miRNA genes, from introns within protein genes, or from polycistronic clusters of closely related miRNA genes. The initial transcripts, pri-miRNAs, are several thousand bases long.
