Bartel research team wins prestigious AAAS Newcomb Cleveland Prize

CAMBRIDGE, Mass. — The discovery of micro-sized RNA molecules (miRNAs)—a breakthrough described as "the biological equivalent of dark matter, all around us but almost escaping detection"—earned the coveted 2001-2002 AAAS Newcomb Cleveland Prize.

Three journal reports, published in the 26 October 2001 issue of Science, were named to receive the Prize, the oldest award conferred by the American Association for the Advancement of Science (AAAS). The AAAS Newcomb Cleveland Prize was established in 1923, with funds donated by Newcomb Cleveland of New York City, to recognize outstanding Science articles.

The award-winning research provides new insights into gene expression–the fundamental process by which information in life's blueprint, DNA, is transferred to messenger RNA (mRNA) and then translated into proteins. Understanding how protein production is controlled during gene expression is essential to unraveling the mysteries of all life processes, including, for example, the development of disease.

The AAAS Newcomb Cleveland Prize was awarded to three research teams at the Dartmouth Medical School in Hanover, New Hampshire; the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology in Cambridge, Massachusetts; and Germany's Max Planck Institute for Biophysical Chemistry.

Together, the winning articles "reveal the completely unexpected abundance of ultra-small RNA molecules, only 20 to 24 nucleotides long," explained Donald Kennedy Editor-in-Chief of Science. "What we've learned is that these abundant microRNAs are evolutionarily conserved across a number of organisms, and may affect gene regulation involved in the development of many types of cells and tissues. The outstanding contributions of these three research teams have thus written a new chapter in our understanding of gene control, and are arguably among the most significant biomedical research papers published in 2001."

In studies of the worm, C. elegans, for example, Rosalind C. Lee and Victor Ambros of Dartmouth were able to clone and verify the expression of 15 miRNAs. Two of these RNAs are also found in humans–including one that may play a role in the development of heart tissue, Lee and Ambros noted.

"Each miRNA is probably matched to one or more other genes whose expression it controls," Ambros said. "Their potential importance to control development or physiology is really enormous. If there are hundreds of these in humans and each has two or three targets that it regulates, then there could be many hundreds of genes whose activity is being regulated this way. It's important to find all the human miRNA genes and understand what they do."

The 2001 Science paper by Lee and Ambros built upon the team's earlier discovery of the first miRNA gene, lin-4, as well as another miRNA, let-7, identified in 2000 by Gary Ruvkun's team at Massachusetts General Hospital in Boston. Worms lacking those RNAs didn't develop properly, prompting further investigation.

At the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Nelson C. Lau, Lee P. Lim, Earl G. Weinstein and David P. Bartel discovered 55 miRNAs in C. elegans, some overlapping those found by Lee and Ambros.

"This regulatory role for RNA–a chemical relative of DNA–appears to have been under-appreciated," Bartel commented. "Until recently, researchers had focused on proteins as gene regulators. We are now exploring how extensively small RNAs are involved in normal gene regulation. This may shed light on what goes wrong in diseases that aren't linked to protein mutations."

At the Max Planck Institute for Biophysical Chemistry, Mariana Lagos-Quintana, Reinhard Rauhut, Winfried Lendeckel and Thomas Tuschl found 14 miRNAs in a fruit fly (Drosophila) embryo, and 19 miRNAs from human cells. Ongoing studies have linked miRNAs with the phenomenon of "RNA interference," a cellular defense mechanism involved in gene silencing.

In a Science Perspective essay on the three research reports, Gary Ruvkun wrote that miRNAs appear to be "the biological equivalent of dark matter, all around us but almost escaping detection."

Throughout the year, Science readers may nominate papers appearing in the journal's research articles, reports, or reviews sections. See the AAAS Newcomb Cleveland Prize website for additional details on the award.