June 24, 1999 CHICAGO --- From just a single fertilized egg, how does Nature produce the cells, bones and organs that make up a human being?
Tissue differentiation, as it is called, results from a highly regulated process that turns specific genes on and off. Unraveling the complexities of gene regulation and protein expression is crucial to scientists' understanding of developmental birth defects and a variety of other medical conditions.
Now, Northwestern researchers have gained new insight into how genes are expressed.
In the June 23 issue of the journal Nature, cell and molecular biologist Elizabeth Goodwin and colleagues at the Medical School described a new role for TRA-1, one of a family of proteins that regulates gene expression by binding directly to DNA, the carrier of genetic material.
The human members of this protein family have been implicated in a number of diseases, including Creig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, postaxial polydactyly type A, and basal cell carcinoma, the most common form of cancer in humans.
"Understanding how this family functions is central to understanding the roles of these proteins in disease," Goodwin said.
Normally, once a gene is activated and its information is transcribed into messenger RNA (mRNA), the 'copy' moves from the nucleus to the cytoplasm of the cell, where the mRNA is 'translated' into a protein.
The investigators found that, in addition to turning genes on, the TRA-1 protein also can regulate the movement of the mRNA from the nucleus to the cytoplasm.
Their experiments confirmed the new role for TRA-1 protein by showing that it binds to a specific region of the mRNA, thus providing an additional mechanism by which cells can fine-tune the level of protein production during embryo development.
Goodwin is an assistant professor of cell and molecular biology at the Medical School and a researcher in the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
This study was supported by grant number GM 51836-01 from the National Institutes of Health and also by Just Cause, a Chicago-based cancer charity.
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