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>  News Releases >   2003 >   February

Geneticists share prize for studies of tiny RNA's

Posted 04/14/03, by Hali Wickner

Victor Ambros and Rosalind Lee of Dartmouth Medical School are among the winners of the Newcomb Cleveland Prize for 2001–2002.
Ambros and Lee honored by American Association for Advancement of Science

The discovery of micro-sized RNA molecules (miRNAs) - described as "the biological equivalent of dark matter, all around us but almost escaping detection" - earned the 2001–2002 Newcomb Cleveland Prize from the American Association for the Advancement of Science for three teams of researchers, including Victor Ambros and Rosalind Lee of Dartmouth Medical School.

The oldest award of the AAAS, the Newcomb Cleveland Prize was established in 1923 with funds donated by Newcomb Cleveland of New York City. Throughout the year, Science readers may nominate papers appearing in the journal's research articles, reports or reviews sections.

Three journal reports published in the Oct. 26, 2001, issue of Science, including one by the DMS researchers, were named to receive the prize, which will be conferred by the AAAS on Feb. 16 in Denver, Colo., to recognize outstanding Science articles. The journal Science also hailed small-RNA discoveries as 2002's breakthrough of the year.

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 Cleveland Prize was awarded to research teams at Dartmouth Medical School; the Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology (MIT); and Germany's Max Planck Institute for Biophysical Chemistry. The period considered covers 12 months spanning 2001 and 2002.

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, Research Associate Lee, and Professor of Genetics Ambros, 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 MIT, 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 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."

-Hali Wickner

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