ONE MAN’S JUNK: Mother Nature’s little helper

Every so often, it is good for us to challenge the so-called truths that we hold dear, for it is often our defense of these truths that keep us from seeing the advantages around the corner. Until Stanley Prusiner and colleagues elucidated the mechanism of prion replication, few of us could conceive of an infectious disease that could propagate without a nucleic acid intermediate. Thalidomide offers a particularly special example of being a wonder drug that was vilified when its use as an anti-nauseate was linked to birth defects. And yet later still, it has seen a renaissanceas scientists have begun to use it as an effective treatment for cancer when proper precautions are followed.

 

But perhaps the one truth that remains most pervasive is the concept of junk DNA; fragments of sequences that lie between the "true" genes of the genome but seem to offer no biological function. In some cases, these chromosome stretches were thought to encode cryptic genes that had been mutated over evolutionary time into silence. Other fragments offered no apparent function, however, now or in the distant past. In The Selfish Gene, Richard Dawkins went so far as to argue that biological organisms were merely vehicles for the propagation of DNA itself. But as with each of the truths that came before it, even the concept of junk DNA is being re-examined.

 

Over the last couple of years, editorial pages have been filled with the exploits of academic and commercial scientists looking to use antisense RNA and RNAi to control gene expression and modulate diseases. But as is so often the case, a good idea developed by humans may already have been put into practice by Mother Nature herself.

 

Recently, scientists have started to find small, naturally occurring RNA molecules that may be involved in controlling the expression of various genes throughout the genome. Unlike the more familiar mRNA, tRNA, and rRNA molecules that directly mediate protein expression by being involved in amino acid assembly, these microRNAs are not directly involved in protein synthesis. Rather, these small (~22-nucleotide) RNA molecules seem to control gene expression by interacting with the mRNA molecules themselves, preventing protein synthesis—a natural parallel to antisense and RNAi. Some scientists have gone so far as to suggest that this former "junk DNA" may be involved in regulating at least 30 percent of all protein genes and play a central role in the pathology of a variety of diseases, including diabetes, obesity, cancer, and certain viral diseases.

 

In announcing the publication of a paper in Nature Genetics that describes their own efforts to expand the number of known microRNA molecules, researchers at Rosetta Genomics expressed their confidence that these natural gene-regulation agents might provide an effective new avenue of drug discovery.

 

"The finding of large numbers of primate-specific microRNAs is exciting because it supports the notion that microRNAs may indeed play an important role in the evolution of complexity in higher organisms," said Dr. Aaron Ciechanover, Nobel laureate and chair of Rosetta's Scientific Advisory Board. "We believe that these genes may serve as an important basis for next-generation diagnostics and therapeutics."

Likewise, at the annual meeting of the International Society for Stem Cell Research in June, researchers from the University of Colorado, Boulder (UCB) and Applied Biosystems described their efforts to use microRNA expression to monitor differentiation in mouse stem cell lines, even to the level of a single cell within a sample.

 

"The different microRNA expression profiles of embryonic stem cells suggest some embryonic cell cultures may contain variable subpopulations of spontaneously differentiated cells," said UCB professor, Dr. William Strauss. "Our newly identified microRNAs could one day be used as molecular markers for monitoring differentiation within embryonic stem cell lines."