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Size doesn't matter

In a story reminiscent of David and Goliath, new research from Rockefeller University shows that sometimes the smallest molecules can be the most powerful. In the July 1 issue of Cell, Ulrike Gaul, Ph.D., and colleagues report that microRNAs serve very important, and very specific, functions during the early development of the fruit fly.

First discovered a few years ago, microRNAs are short strings of RNA that are made in large amounts in every cell from plant to humans. Biochemists, including co-author Thomas Tuschl, Ph.D., found that microRNAs bind to messenger RNAs, which are the blueprints for proteins, and either target them for destruction or inhibit them from making proteins.

"There was a lot of beautiful biochemistry showing how microRNAs are made and processed," says Gaul, head of the Laboratory for Developmental Neurogenetics. "But we didn't really know how important they are for the development of an organism and its function."

To solve this question, Gaul and colleagues systematically blocked each of the 46 known microRNAs that are active during early development of the fruit fly. This is difficult to do by traditional genetic means, so they inject young fly embryos with short strings of RNA that bind to the microRNAs and prevent them from finding their target messenger RNAs. The researchers found that over half of the microRNAs were not only essential for development, but also affected it in very specific ways.

"Many of the fundamental processes in development are regulated by microRNAs," Gaul says, "including body patterning, morphogenesis, nervous system and muscle development. In particular, though, we found that cell survival relies very heavily on them."

Cell death in development is not uncommon. The developing embryo makes an overabundance of many cell types, like nerve cells, which it then removes later in a process of fine-tuning. In fact, the genes in flies that carry out a cell's death sentence, Hid, G
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Contact: Kristine Kelly
kkelly@rockefeller.edu
212-327-7146
Rockefeller University
1-Jul-2005


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