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Jefferson researchers uncover new way nature turns genes on and off

Peering deep within the cells of fruit flies, developmental biologists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia may have discovered a new way that genes are turned on and off during development. If they're right, and the same processes are at work in higher organisms, including mammals, the findings could eventually have implications for improving the understanding of a range of diseases, including childhood cancer.

Reporting in the journal Cell, Alexander Mazo, Ph.D., professor of biochemistry and molecular biology at Jefferson Medical College, Svetlana Petruk, Ph.D., and their co-authors focused on pieces of genetic material called non-coding (nc)RNAs. About two-thirds of the human genome is converted into such RNAs (the better known messenger RNAs are translated into proteins), though the function of the majority is unknown. The researchers detailed a possible mechanism by which ncRNAs briefly control the functioning of homeotic, or HOX, genes, which guide the master developmental plan of the organism.

"We think that this new mechanism operates early in embryogenesis," says Dr. Mazo.

According to Dr. Mazo, the researchers found that one of the likely mechanisms behind ncRNAs' ability to regulate essential coding genes is through a "transcription interference" mechanism. "Such mechanisms are known in bacteria and yeast, but not much is known in higher organisms," he explains.

In the fruit fly, HOX gene activity is maintained by genes and proteins in the Trithorax group (TrxG). These proteins are thought to act through so-called maintenance elements, one of which, in a nearby region, bxd, is located between two HOX genes, Ubx and abd-A. Dr. Mazo explains that several "long" ncRNAs are transcribed through bxd maintenance elements. They were thought to be expressed in the same cells as Ubx, and to regulate HOX gene coding sequence expression. But the researchers found something different: ncRNAs i
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Source:Thomas Jefferson University


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