The second DNA string is also important

The FANTOM Consortium for Genome Exploration Research Group and Karolinska Institutet announce the publication of “Antisense Transcription in the Mammalian Genome” in Science, September 2nd 2005.

It has been known for over half a century that our genetic material occurs as a double strand of DNA molecules. Only one of these strands – the so-called sense strand – encodes for proteins, the building blocks of our cells that in turn make up our bodies. Then what about the other DNA strand – the antisense strand – can it also exert functions? The answer is yes, it can produce so-called antisense genes that are read in our cells in the opposite direction of the real – sense – genes. This phenomenon has previously been regarded as rare, but scientists now show that it is actually the rule rather than the exception. More importantly, these antisense genes are now shown to be extensively used to modulate the expression of the conventional – sense – genes in our cells. Antisense genes are therefore likely to participate in the control of many, perhaps all, cell and body function.

These findings are also of interest because synthetic – man made – antisense molecules have been widely used to inhibit conventional genes, including applications as anti-viral and anti-cancer drugs, which are currently on the market or in clinical trials. It can now be argued that this same principle already has been used by nature on a massive scale.

Many of the described antisense genes are also unusual because they do not encode for proteins and therefore do not fit into the classical definition of a gene. This concept of non-protein-coding RNA is supported by the data in an accompanying report entitled “The Transcriptional Landscape of the Mammalian Genome” by the FANTOM Consortium in the same issue of Science. Since mammals, like humans and mice only have slightly more conventional genes (around 22,000) than a simple worm, the results clearly indicate that while proteins comprise the essential components of our cells, the development of multicellular organisms like mammals is controlled by vast amounts of regulatory noncoding RNAs that until recently were not suspected to exist or be relevant to our biology. Moreover, since most proteins are similar among mammals it also suggests that many of the differences between species may be embedded in the differences in the RNA regulatory control systems, which are evolving much faster than the protein components.

If correct, these findings will radically alter our understanding of genetics and how information is stored in our genome, and how this information is transacted to control the incredibly complex process of mammalian development, with implications for the future of biological research, medicine and biotechnology.

Both of these publications are part of a long-standing international effort and represent an enormous body of work.