Scientists Find They Can Tap Gene-Silencing Process To Reveal Parts Of Genetic Machinery

RNA interference -- RNAi for short -- works in animal cells by degrading the messenger RNAs that serve as the mobile blueprints produced by genes.

Now, scientists at the University of North Carolina at Chapel Hill have discovered that RNAi itself can be exploited to rapidly identify parts of the machinery that make RNAi work. With further research, the finding might have important implications for treating cancer and other serious illnesses, they say.

“We stumbled upon the finding,” said Dr. Robert P. Goldstein, assistant professor of biology. “A graduate student in my lab, Nate Dudley, found that what was considered an annoying peculiarity of RNAi became, in the end, a really useful way to figure out how it works.”

A report on the discovery appeared online in the March 19 early edition of the Proceedings of the National Academy of Sciences and will appear in the April 2 print issue. Dudley, Goldstein and biology postdoctoral fellow Jean-Claude Labbe carried out the research and wrote the paper.

The team conducted its experiments in one-millimeter-long worms that live in soil and eat bacteria. Scientists call the critter Caenorhabditis elegans.

“The coolest thing about C. elegans is that it has all the major cell types that we have -- muscle, nerve, gut, skin and so on -- yet the whole worm contains only 959 cells,” said Goldstein, a member of the Lineberger Comprehensive Cancer Center at UNC’s medical school. “C. elegans is therefore one of the simplest organisms available for studying how genes function during development. Human beings, on the other hand, have trillions of cells.”

Many experiments, which would take forever or be impossible or unethical in humans can be done rapidly in C. elegans, he said. Eventually, scientists will determine if what they learn from the worm model applies, as they expect, to mammals and humans as well.

“The worm is optically clear so that we can see everything going on inside, and it goes through a complete generation in only three days,” Goldstein said. “It was the first animal in which the complete genome was sequenced, and it is used by a several hundred labs around the world to study an incredibly diverse array of biological phenomena, including aging, cancer and cell death.”

Injecting pieces of laboratory-produced, double-stranded RNA into the worms, the researchers could “silence” just about any gene they wanted depending on the composition of the RNA they chose, he said.

“What we found was that if we silenced the activity of genes that are part of the RNA interference mechanism, we could turn off the RNA interference,” he said. “Since only a few pieces of the RNA interference machinery are known right now, we can use this method to identify more pieces of the mechanism.”

Once that process is mostly or entirely understood, scientists should be able to turn off gene expression at will, including genes responsible for cancer and various genetic disorders.