Until the 1980s, researchers believed that protein enzymes alone catalyzed the chemical reactions essential for cellular survival. Since then, rare RNA catalysts known as ribozymes have emerged, showing biologists that, in addition to storing genetic information, RNA can also catalyze chemical reactions. However, researchers have struggled to explain the full biological story of these elusive RNAs, identifying just 2 classes of ribozymes in the past 25 years.
Using bioinformatics methods, Yale researchers recently tracked down a new class of small self-cleaving ribozymes they call “twister.” Named after its Egyptian “twisted flax” hieroglyph shape, nearly 2700 types of “twisters” reportedly occupy a wide variety of bacterial and eukaryotic species.
“One could show a bacterium, a parasitic wasp, and a rice plant and see that these things are everywhere,” said Ronald Breaker, a Professor of Molecular, Cellular, and Developmental Biology at Yale University who led the study, which was published in Nature Chemical Biology.
To capture “twister,” Breaker’s group combed through extensive genomic data using algorithms to identify similarly sequenced, highly conserved RNA structures common across different species. The team then identified an unusually shaped RNA structure located near other known self-cleaving ribozymes within different genomes.
“We looked at our bioinformatics data, and we knew where in the genomes this was,” said Breaker. “We knew that there was another type of RNA that had that same pattern, so we were able to guess its function, and we got it.”
Although identified by similar features, Breaker noted that this class of ribozymes functions quite differently from other known types of ribozymes, suggesting that “RNA has many different ways to solve the same problem. That bodes well for the RNA world theory, which holds that at one time RNA was calling all the shots.”
While a picture of that RNA world is currently far from complete, this new approach should introduce several more players. “Now we think we know where to look for self-cleaving ribozymes. We know where they hide, and we are certainly going to find more,” added Breaker.
Roth A, Weinberg Z, Chen AG, Kim PB, Ames TD, Breaker RR. A widespread self-cleaving ribozyme class is revealed by bioinformatics. Nat Chem Biol. 2014 Jan;10(1):56-60.