Yale scientists find cooperative RNA switches in nature

Research at Yale reported in the journal Science identifies a new riboswitch (RNA regulatory sequence) class in bacteria that operates as a rare “ON” switch for genetic regulation of the three proteins in a glycine processing system.

“This seems like something only a biochemist can appreciate, but what it really means is that modern RNA has what it takes to run the complex metabolism of life. It is like what would have been needed in an “RNA World” – or a period in evolution where RNA served a much larger role,” said Ronald T. Breaker, professor in the Department of Molecular, Cellular and Developmental Biology at Yale University.

The latest riboswitch is unique because it is the first RNA switch known to have “cooperative binding” to its target, a process that is common in protein enzymes but not usually associated with RNA. It is also surprising that such complex relics of an RNA World are seen in modern organisms.

Breaker and his research team have pioneered the field of riboswitches and reported the existence of nine classes, so far. Earlier this year they reported in the journal Nature on a class of riboswitch that are ribozymes and catalyze their own feedback loop. The work received the highest all time rating of a peer-reviewed scientific paper by the Faculty of 1000, an on-line web resource where top researcher from around the world rank scientific publications

Breaker’s research, testing theories about how life began, led to the synthesis of “RNA switches” that respond to various target compounds, including several molecules of basic metabolism. They speculated that, if an RNA World theory were true, then RNA molecules most likely would make great molecular switches. After creating RNA switches in the lab, including using a process that simulates Darwinian evolution in the test tube, they looked for naturally occurring riboswitches.

Other authors on this paper include Maumita Mandall, Mark Lee, Jeffrey Barrick and Gail Mitchell Emilsson from Yale and Zasha Weinberg and Walter L. Russo from the University of Washington. The work was supported by grants from the National Institutes of Health, the National Science Foundation, the Yale Liver Center and the David and Lucille Packard Foundation.