So we finally thought we knew something about genetics. Due to unpredictably advanced computer processing capabilities, the Human Genome Project approached the finish line well ahead of schedule (perhaps a record for a government project!), and we all decided that it would now be a simple matter to translate this information into cures for all diseases known to man. Of course, this translation has not been so smooth. Human disease is a complex affair. Single mutations may or may not cause a change in the production of a protein which may or may not have some impact on the evolution of a disease process, depending upon interactions with any of a number of other genetic, post-transcriptional proteonomic or environmental factors.

Back in the pre-internet days of my medical school education, we were taught that the DNA was composed of four building blocks, called nucleotides (actually two pairs) whose sequence would then be transcribed by a messenger RNA which would deliver the “message” to the protein producing part of the cell where, 3-by-3 these sequences would designate the amino acid structure that would build the proteins—the key molecules that served as structural building blocks and physiologic intermediaries (e.g. enzymes) that would direct the process of life within the organism. Mostly true, but not nearly so simple. The real story is well beyond the scope of this article. Suffice it to say, there are certain key pieces of information missing from this paradigm.

Let’s leave aside for a moment the complex issues of which portion of the DNA gets exposed (and when and how and what turns this process on and off), and merely contemplate for a moment that the vast majority of DNA does not encode for any proteins whatsoever. Perhaps if you are an evolutionist you might conclude that this “junk” DNA is merely the remnant of our phylogenetic past. However, what we at the Florida Heart Research Institute, are learning, along with our genetic collaborators at the University of Miami, and with the rest of the scientific world, is that these vast stretches of DNA, rather than being “junk” or evolutionary waste, actually comprise an incredibly complex and ingenious control mechanism which helps to regulate what genes get “turned on” and which ones get “turned off” and when. Recent years have welcomed the discovery of what is termed “micro RNA.” These short peptide sequences actually correspond to critical areas of messenger RNA and, when released, can bind to that RNA, thereby blocking it from its function of serving as a template for protein synthesis. Other micro RNA’s can serve a promotional rather than inhibitory function.

Why do we need these things? Never underestimate the wisdom or complexity of living systems. Certain situations may call for the production of one or more proteins. Wouldn’t it be “nice” if we could summon all the elements necessary for a process at the same time when we want to? If we don’t need them in equal quantities, then we just modify the request. If we don’t need them forever (so we really don’t want the “on” switch to stay “on” forever), then we just modify the request when we want something slowed down or turned off. If we need some in a hurry and others won’t be needed until later, we just indicate which ones are needed first, and how fast, which ones second, etc. Now you can begin to appreciate the complex regulatory framework within which the genetic mechanism operates.

Florida Heart recognizes that micro-RNA’s are one of the key novel regulators which are increasingly being appreciated to play key roles in human disease. In the future, it is not hard to imagine, that once we have a better understanding of the elements controlling a process, we will be better able, possibly by strategic introduction of or inhibition of specific micro-RNA’s to regulate some of the key processes in the evolution of cancer, cardiovascular and other diseases. We just need to be careful about how and when we chose to shoot the messenger.