by Benjamin Tran
While at the Carnegie InstitutionÕs Department of Embryology in Baltimore, Andrew Fire, currently a Stanford professor in the School of Medicine, and Dr. Craig Mello from the University of Massachusetts Medical School, elucidated a mechanism by which cells can inhibit the translation of mRNA into proteins. For their discovery of RNA interference in 1998, Fire and Mello were awarded the 2006 Nobel Prize in Physiology or Medicine.
Working with Caenorhabditis elegans (C. elegans)Ña type of nematode, they found that injection of short, double stranded RNAs (dsRNAs) that complimentarily match the sequence of a particular gene interfere with the production of that gene product, thereby silencing the gene. This Ògene knockdownÓ behavior had been previously observed by plant biologists, but the exact mechanisms were unknown. While trying to increase the color intensity of petunia petals by injecting a color-inducing gene, plant biologists had found that this actually led to a complete loss of color.
As Fire and Mello explain in their seminal Nature paper, RNA interference was not only potent but also target-specific. Subsequent research indicated that the dsRNA activates an enzyme called Dicer that cuts the dsRNA into smaller segments. The segments connect with proteins to form RNA-induced silencing complexes that cleave and degrade complementary matching strands of mRNA. As a result, the mRNA is not translated, and no protein product is produced.
RNA interference is significant because scientists can use it to quickly study the functions of particular genes. Previous to RNA interference, if a researcher wanted to elucidate the function of a specific gene, he would have to spend weeks, months, or even years developing a "knockout" - a cell or organism engineered so that it is missing that particular gene. Now, if a researcher wants to study the function of a gene, he just needs to add the complimentary RNA sequence to that cell or organism.
Currently, research is being performed in Fire's lab to elucidate the actual biophysics and signal pathways of the RNA interference seek-and-destroy mechanism. Fire comments on the future of RNA interference: ÒGetting a very detailed and clear picture of what RNA interference does for cells will be interesting to see."