“Amazing” RNAs found to play a more complex role than though

Any biology textbook will depict proteins as the workhorses that carry out the lion’s share of biochemical reactions in cells. Aside from a few exceptions, however, RNAs have largely been pigeonholed as passive middlemen between DNA and proteins.

New findings from the laboratory of Ronald Breaker, Ph.D., Henry Ford II Professor of Molecular, Cellular, and Developmental Biology, and Howard Hughes Medical Institute Investigator, suggest that RNAs play a more complex role than previously thought, and that, in certain tasks in certain organisms, they take on a more dominant role than proteins. Breaker and colleagues have discovered a slew of large RNAs that do not code for proteins but in-stead form complex three-dimensional structures in simple organisms like bacteria—structures that may carry out complex biochemical functions. “Every time we feel as though we’re giving RNA just about the right amount of credit, we find more amazing RNAs,” said Breaker. “I think this is just a continuation of the data that forces us to move our standards ever higher for what we think RNA should be able to do.”

First author Zasha Weinberg, Ph.D., a postdoc in Breaker’s lab, and colleagues reported in the December 3 issue of Nature on several new large noncoding RNAs in bacteria, two of which the research team christened GOLLD and HEARO. Preliminary work suggests that GOLLD helps viruses that infect bacteria to burst out of infected cells so that they can seek new targets, whereas HEARO might be a mobile genetic element, which are present in all organisms and a cause of spontaneous genetic change.

Breaker’s group culled these and other noncoding RNAs out of stretches of “junk DNA” that do not code for proteins. The researchers matched junk DNA sequences between related bacteria to identify stretches that were highly conserved—a red flag that signals evolutionary preservation and perhaps importance. They then looked at these conserved DNA sequences to pick out regions that, when transcribed into RNA, could form complex RNA structures—hairpins, loops, and knots—enabling them to sift out the probable noncoding RNAs.

Breaker hasn’t determined whether these noncoding RNAs represent living relics of an ancient RNA-centered world that might have existed before proteins evolved and drove many catalytic RNAs to extinction, or whether they represent more modern developments.

Whatever their origin, given the number of noncoding RNAs that Breaker suspects may be active in select organisms, he feels it is important to come to grips with how modern cells really function. “It’s not that the science that we know about modern cells is wrong, but as we find more and more noncoding RNAs, we recognize how incomplete our understanding is,” Breaker said.