Much of the daily business of life is catalyzed by enzymes, but certain RNA molecules can also speed up chemical reactions. Now scientists have found that even RNA molecules made with just two nucleotides, or "letters," instead of the usual four, can do the trick. The ability of an artificial, stripped down RNA molecule to function as an enzyme might bolster a popular theory that RNA molecules dominated the early history of life on Earth.
RNA molecules help "read" DNA and transform genetic information into workhorse proteins. In recent years, scientists have come to believe that RNA may once have been far more than a middleman. Early in life's history, RNA might have catalyzed critical chemical reactions to sustain an organism, doing the jobs of both DNA and proteins. This "RNA world" theory has been bolstered by evidence that some RNA molecules can duplicate others--a key task normally performed by proteins (ScienceNOW, 17 May 2001).
Biochemist Gerald Joyce of the Scripps Research Institute in La Jolla, California, and postdoctoral student John Reader wondered whether a more primitive RNA molecule resembling a hypothetical RNA precursor could trigger this same reaction. To find out, they created stretches of RNA made up of two nucleotides: adenine and uracil, or "a" and "u." But how best to order them? For that, Joyce and Reader relied on Darwinian selection to find the "fittest" of the nucleotide arrangement. They created 100 trillion versions, each with about 75 letters.
The result: a tiny fraction, roughly 1 in a billion, were able to replicate themselves. Picking one of the better performers, the scientists studied it more carefully. Reporting in the 18 December Nature, they note that although it replicated, it did so at a sluggish rate, between 1000 and 1 million times slower than a normal enzyme.
"It's amazing that you can get catalytic activity with just two nucleotides," says Harvard molecular biologist Jack Szostak. Still, he adds, it's unclear whether that suggests two-nucleotide RNAs were prominent years ago, because their activity is so slow. To answer that question, says Szostak, researchers need to see whether they can experimentally speed up the molecules' behavior.