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RNA editing process plays essential role in embryo development

In a new study, scientists at The Wistar Institute report the first direct evidence that RNA editing is essential to mammalian embryo development. RNA editing is a normal but not yet fully understood process in which small nucleotide changes occur after DNA has been transcribed into RNA. The process makes it possible for one gene to be translated into multiple proteins with different structures or functions.

The researchers repeatedly attempted to delete, or knock out, in mice a gene known to be involved in RNA editing called ADAR1 in order to study its function. Certain target genes in the brain are known to be subjected to RNA editing by the ADAR1 enzyme, including glutamate receptor ion channels, critical for memory formation, and serotonin receptors, which regulate emotional behaviors. The investigators expected that deletion of the ADAR1 gene would therefore lead to significant changes in brain functions.

Unexpectedly, however, they found that the knockout mouse embryos died midterm due to an inability to make mature red blood cells. At the least, the results suggest that ADAR1 and RNA editing are critical to the development of mature red blood cells, an essential step in mammalian embryo development. The new findings were published in the December 1 issue of Science.

"The inability of mice with a defective RNA editing system to make mature red blood cells is likely just the tip of the iceberg," says Wistar professor Kazuko Nishikura, Ph.D., senior author on the study. "The ADAR1 gene is expressed in many tissues throughout the body in addition to the brain and is probably involved in the RNA editing of a number of target genes that have not yet been identified."

As scientists prepare to enter the post-genomic era, the role of RNA editing in determining protein structure and function may become an increasingly important consideration in genetic research. Investigations such as Nishikuras indicate that RNA editing is fundamental
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Contact: Marion Wyce
wyce@wistar.upenn.edu
215-898-3943
The Wistar Institute
30-Nov-2000


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