Amidst the increasing attention given to the economical sequencing of the human genome, one inconvenient truth remains largely ignored. Virtually all of biomedical science and pharmaceutical industry has focused on merely 2% of the genome, the segment of the genome that encodes proteins. Until recently the other 98% had been somewhat famously described as Junk. However, it is now clear that non-coding RNAs such as microRNA, esiRNAS, piRNAs that reside in the “junk”, have critical cellular functions.
It has been known for a long time that it is the noncoding segment of the genome that is most variable between human individuals. Thus, when the deluge of human sequence information arrives, the successful interpretation of these variants will be a challenge. However, noncoding RNA genes appear to exert their effect by their complementarity to other nucleic acid sequences and therefore their interactions are much more predicable than their protein counterparts
For example investigators have begun to explore the possibility that variants in human sequence may affect phenotype by modulating microRNA target sites in messenger RNA. Indeed, Dr Francis Collins, the new NIH director has recently written a timely and compelling review of this area.
Importantly, it is critical to realize that these human sequence variants are “plastic”. Their ability to increase the risk of disease is not “cast in stone’ but will depend upon the expression of the noncoding RNA. It is hoped that an understanding of the factors that regulate such noncoding RNAs will identify changes in life style that may prevent disease.