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Structure solved by Scripps scientists shows one way that body controls gene expression

A group of scientists at The Scripps Research Institute has solved the structure of a protein that regulates the expression of genes by controlling the stability of mRNA -- an intermediate form of genetic information between DNA genes and proteins.

"Gene expression can be controlled at many levels, " says Scripps Research Professor Peter Wright, Ph.D., who is chairman of the Department of Molecular Biology and Cecil H. and Ida M. Green Investigator in Medical Research at Scripps Research. "One of them is at the level of the message."

The structure of the "tandem zinc finger" domain of the regulatory protein TIS11d in complex with a strand of mRNA was solved in the laboratory of Wright and H. Jane Dyson, Ph.D., by Maria A. Martinez-Yamout, Ph.D., of Scripps Research, and Brian P. Hudson, Ph.D., of Rutgers University. This is the first such structure to be solved, and it provides insights into the process of gene regulation at the atomic level.

In next month's issue of Nature Structural & Molecular Biology, Wright and his colleagues describe the tandem zinc finger -- thus called because it contains two finger-like domains that must bind to zinc to fold into its active form. These tandem zinc fingers are a very common motif in mammalian genes, and hundreds of genes in the human genome contain some version of them. This diversity is perhaps indicative of the capability of TZF proteins to specifically recognize a large number of different RNA sequence motifs.

Insights into the workings of the regulatory protein TIS11d are particularly valuable because these proteins are involved in a number of fundamental biological processes, such as inflammation, and are potential targets for therapeutics in diseases where these processes go awry.

The Regulation of Genes at the mRNA Level

Regulation of gene expression in humans and other organisms is a crucial part of biology, and biology has a
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
13-Feb-2004


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