Nobel Laureates Andrew Fire and Craig Mello

The Nobel Prize in Physiology or Medicine 2006

"for their discovery of RNA interference - gene silencing by double-stranded RNA"

Craig Mello (left) and Andrew Fire (right) won the Nobel Prize in 2005 for discovering RNA interference in Caenorhabditus elegans. The mechanism involves synthesis of a double-stranded RNA molecule where one of the strands is identical to the coding region of a protein-coding gene and the other strand is a complementary antisense RNA. The double-stranded RNA binds to a protein complex called Dicer, which degrades the "coding" strand RNA leaving a small antisense siRNA. This RNA binds to a RISC complex that seeks out the mRNA that's complementary to the antisense RNA and cleaves the mRNA. (RISC = RNA-induced silencing complex.)

The interference mechanism blocks the synthesis of proteins from the target RNA. It is used to block synthesis of viral proteins following infection and to block synthesis of transposon proteins.

Here's part of the Ceremony Speech.

THEME:
Nobel Laureates

Fifteen years ago, we thought we knew enough about the flow of genetic information to use it for practical purposes. But we did not achieve the expected results. Attempts to silence a gene in an experimental animal were sometimes fruitless, and attempts to use gene technology for improving the colours of flowers could even cause the plants to lose colour completely. These results perplexed the scientific community. Was there an unknown regulatory step on the way from DNA to protein?

This enigma was solved by the 2006 Nobel Laureates, Andrew Fire and Craig Mello. They suspected that RNA contained the solution to the problem and decided to test it in a simple model organism, the nematode worm Caenorhabditis elegans.

Fire and Mello injected different types of RNA into the worms – and usually nothing happened. But they also made the ingenious decision to mix two RNA molecules in a test tube before injection. One RNA molecule was an exact copy of a messenger RNA and the other a mirror image of the messenger. In the test tube, the two RNA molecules bound to each other and formed a double strand. Injection of that double-stranded RNA led to the silencing of the gene. Fire and Mello had discovered a new mechanism for controlling the flow of genetic information.

In their brilliant paper from 1998, Andrew Fire and Craig Mello demonstrated that double-stranded RNA activates an enzymatic mechanism that leads to gene silencing, with the genetic code in the RNA molecule determining which gene to silence. Today, we call this mechanism RNA interference.

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Photo Credit: The figure is from the Nobel Prize press release.

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