Discovery of naturally occurring RNA "switches" that manage the amino acid glycine

Two University of Washington computer scientists are part of a team that has discovered a pair of rare, naturally occurring RNA "switches" in a class of bacteria that work cooperatively to manage the amino acid glycine.

The finding, reported in the current issue of the journal Science, could support the notion of an "RNA world," or an evolutionary period when RNA played a much greater role in metabolic processes.

RNA stands for ribonucleic acid, a chemical that is found in cells. Its main role lies in transmitting genetic instructions from DNA to the rest of the cell and controlling certain chemical reactions.

The newest riboswitch, as it's called, is unique because of its cooperative nature, representing a complex mechanism previously found only in protein enzymes.

"The current world has a combination of proteins and nucleic acids, including RNA, playing a role in life, and there is an immense chicken-and-egg problem because you can't have one without the other," said Walter Ruzzo, a professor in the UW's Department of Computer Science & Engineering with an adjunct appointment in the Department of Genome Sciences. "One theory, and it's still controversial, is that RNA played both roles at one point."

Ruzzo and Zasha Weinberg, a CSE graduate student, have been working with a group of biochemists from Yale University since February, looking for RNA switches in nature. The Yale researchers had already identified the switch in question, but hadn't yet realized what they had.

That's where computer science came in. The use of computing technology to examine and compare the RNA structures is critical to the work, Ruzzo said.

"The key to understanding these things is to find more examples of them, and Zasha has developed some terrific computational tools that speed up the search for these structures," he said. "Because Zasha had a much more sensitive searching tool, he found that these switches usually appear in tandem. They have the same structure, but they are significantly different at the nucleotide level. The biochemists simply didn't see that they came in pairs."

The net effect of having the pair working together is that it provides a much more efficient switch in detecting glycine.

Glycine is a building block for protein, but it can also be used for energy. The double switch is able to strike the right balance between having enough glycine for protein synthesis and being able to readily use any extra for energy production.

"The cooperation means that the switch turns more sharply from off to on when an excess of glycine is created," Ruzzo said.

The senior author of the paper is Ronald Breaker, professor in the Department of Molecular, Cellular and Developmental Biology at Yale. Other authors, also from Yale, include Maumita Mandal, Mark Lee, Jeffrey Barrick and Gail Mitchell Emilsson.