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It remains a mystery how humans, with roughly the same number of genes as, for instance, puffer fish, are able to develop the complex brain that characterizes our species. Some researchers, among them James Deshler, an assistant professor of biology, suspect that the answer may lie not in the types and numbers of genes, but in how human cells regulate the synthesis of proteins (gene products).
Within the nucleus of each cell, genetic information is transcribed, copied from DNA to messenger RNA (mRNA), designed to carry the code from the nucleus into the cytoplasm, where proteins are synthesized. Deshler and his colleagues have been studying a mechanism, known as RNA localization, by which cells control how sites within their cytoplasm are targeted by specific mRNA for synthesis of distinct proteins.
In a growing embryo, for example, nerve cells (neurons) direct some mRNAs to axons, the long, threadlike part of the neuron that carries nerve impulses away from the cell body and toward a target tissue, such as muscle, skin, or the brain. These cells develop high concentrations of specific proteins in the axon, which allows the neuron to follow chemical cues and grow toward its particular targets.
Deshler and his colleagues in the Bioinformatics Progam developed a novel computer program, dubbed REPFIND, that recognizes sequences in the mRNA that control RNA localization with unprecedented reliability (100 percent thus far). The researchers first demonstrated the program’s capability of recognizing RNA localization signals in frog genes. They then scanned the entire human genome and found that RNA localization signals are three times more common in human genes than in frog genes, and that many of the human RNA localization signals are found in genes that facilitate axon guidance during neuronal growth. This, the researchers suggest, may be a key element responsible for establishing the complicated neuronal circuitry characteristic of the human brain.
A paper describing REPFIND was published
in the October 15, 2002 issue of the journal Current Biology.
In addition to Deshler, the authors include J. Nicholas Betley
(CAS’01), a research technician who began this work
as a Undergraduate Research
Opportunities Program student; Martin Firth (ENG’04),
a graduate student in bioinformatics; Joel Graber, an ENG
bioinformatics research assistant professor; and Stephanie
Choo (GRS’04), a student in the graduate program in
molecular biology, cell biology, and biochemistry.
Image: RNA (Red) localizing in a growing frog oocyte. The hole in the middle is the large nucleus or germinal vesicle typical of these single cells. |
