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Biological Chemistry

RNA Interference

Two Americans share prize for discovery of RNA gene-silencing mechanism

by Celia Henry Arnaud
October 9, 2006 | APPEARED IN VOLUME 84, ISSUE 40

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Credit: Stanford University School of Medicine
Fire
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Credit: Stanford University School of Medicine
Fire

The 2006 Nobel Prize in Physiology or Medicine honors the discoverers of RNA interference, the gene-silencing mechanism in which double-stranded RNA instigates the degradation of messenger RNA from specific genes. Biologists Andrew Z. Fire of Stanford University School of Medicine and Craig C. Mello of the University of Massachusetts Medical School, Worcester, will split the prize, worth more than $1.3 million.

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Mello
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Mello

RNA interference, or RNAi, which prevents genes from being translated into proteins, is "one of the most significant discoveries in the past 50 years. It's opened up so many avenues for research, for therapeutics, for thinking about evolution," says John J. Rossi, a molecular biologist at Beckman Research Institute of the City of Hope in Duarte, Calif. "It may not have been as profound as the discovery of the structure of DNA, but it's implications are as far-reaching."

Fire and Mello unearthed RNAi while studying the regulation of gene expression in the worm Caenorhabditis elegans. When the mRNA for making a muscle protein and the complementary noncoding strand of RNA, the so-called antisense RNA, were injected together, the worms behaved as if they didn't have the functioning muscle protein.

The complementary RNA strands had combined to form double-stranded RNA. When Fire and Mello injected various double-stranded RNA molecules into their worms, they found that the RNA silenced the genes containing those specific codes (Nature 1998, 391, 806).

Since the original discovery, scientists have shown that during RNAi the double-stranded RNA guides the target mRNA to a protein complex known as the RNA-induced silencing complex, which cleaves and thereby inactivates the mRNA.

RNAi, which has also been shown to work in mammalian cells, is now a broadly used research tool for studying gene function. It is also under intense investigation as a potential therapeutic approach for silencing genes responsible for illnesses.

For researchers in the RNAi field, the only surprise about last week's announcement is how quickly it came after the initial discovery. "RNAi is a very young field. Things have gone incredibly quickly," says Phillip D. Zamore, an RNAi expert and one of Mello's colleagues at the University of Massachusetts Medical School. "If you [had asked] anybody who was going to win the Nobel Prize for RNAi, everyone would say Fire and Mello. It's so obvious that their 1998 Nature paper changed our whole perception from something weird in worms to real biology."

"Over the past few years, it's become clear that this [prize] was likely to happen one day in the not-too-distant future," says Jeremy M. Berg, director of NIH's National Institute of General Medical Sciences, which supports research by both Fire and Mello. "The impact of RNAi has been so dramatic already, and it's only getting stronger."

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