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Once given 'no respect,' cells' tiny RNAS take driver's seat

Ribonucleic acid, or RNA, has long been thought to be important only to translate a gene's DNA into the proteins that are cells' workhorses. But new evidence shows that tiny bits of RNA not used to make proteins actually play central roles in normal biology and in the development of cancers.

"Scientists have known for a few years that production of these tiny RNAs, known as microRNAs, is only supposed to happen at certain times and in certain tissues, but no one had been able to identify what controlled the timing," says Joshua Mendell, M.D., Ph.D., assistant professor in the McKusick-Nathans Institute of Genetic Medicine. "We've identified the first such controller, a well-studied protein called Myc. Our discovery fits in quite well with the two other labs' studies on the involvement of microRNAs in cancer."

The work from investigators at Johns Hopkins is one of three papers on microRNAs in the June 9 issue of Nature.

Identified only a few years ago, microRNAs' best-known function is to control the extent to which other genes can be used to make proteins, by binding to and interfering with genes' protein building-instructions. The microRNAs play roles in cell division, cell specialization and cell death in worms and flies and are off-kilter in human cancers, but the Myc protein is the first factor identified that controls the production of microRNAs.

Myc (pronounced "mick") is already known to regulate about 10 percent to 15 percent of the genes in the human genome, controlling the extent to which they are used to make proteins. Myc also is faulty and overactive in many human cancer cells, although exactly how it contributes to cancer is unclear.

Given Myc's regulatory role and its involvement in cancer, the Hopkins researchers tested human cells to see whether changes in the amount of Myc affected levels of any of the more than 200 known microRNAs. Through these experiments and others, they discovered that Myc directly controls t
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
8-Jun-2005


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