Andrew Fire and Craig Mello have won the Nobel Prize in Medicine for the discovery of RNA interference:
Americans Andrew Z. Fire and Craig C. Mello won the Nobel Prize in physiology or medicine Monday for discovering a powerful way to turn off the effect of specific genes, opening a new avenue for disease treatment.
”RNA interference” is already being widely used in basic science as a method to study the function of genes and it is being studied as a treatment for infections such as the AIDS and hepatitis viruses and for other conditions, including heart disease and cancer.
Fire, 47, of Stanford University, and Mello, 45, of the University of Massachusetts Medical School in Worcester, published their seminal work in 1998.
RNA interference occurs naturally in plants, animals, and humans. The Karolinska Institute in Stockholm, which awarded the prize, said it is important for regulating the activity of genes and helps defend against viral infection.
RNA interference is an only recently understood — and frankly peculiar — way of regulating the expression of genes. It was originally discovered because if you insert double stranded RNA (dsRNA) into cells you get a generalized destruction of RNAs and cessation of protein synthesis. This is because dsRNA in cells is associated with viruses — it shouldn’t be there and the cell knows it.
More interestingly, dsRNAs were shown to have some gene specific effects in cells where the viral suppression was not an issue — in stem cells and the like.
It works something like this. Figure is from here (click to enlarge).
dsRNAs whether artificially introduced (by the experimenter) or created by the cells are chopped up into tiny pieces by a protein called Dicer. They then go to bind a complex called RISC where they can have a variety of effects on mRNAs with sequences similar to them. They can suppress translation of new proteins. They can cause the degradation of those mRNAs. They can induce chromatin modification at the points in the genome where those mRNAs were generated, causing long lasting changes in transcription. All of these have the effect of downregulating the activity of particular genes with similar sequences to the tiny dsRNA.
This was a huge discovery for two reasons.
1) It produced an invaluable experimental tool. Using RNAi, researchers can specifically knockdown the production of any protein in a cell. This is important for use in cells for which transgenics that lack that protein cannot be easily created.
2) It opens up a huge new level of regulation in the human genome. For many years, we thought the regions of the genome that did not code for proteins — called introns — were just junk DNA. It turns out that much of this DNA codes for RNAi elements. Interestingly, each little RNAi sequence can downregulate not only one gene, but an entire class of genes through sequence similarity. This means that the expression of these tiny RNAs might have more to do with maintaining the developmental state of a cell than the expression of any individual gene. Scientists are, as we speak, trying to figure out how this whole business works.
Congratulations, Drs. Fire and Mello.