Over and over in his 19-year career at Yale, Ronald R. Breaker, Ph.D., chair and Henry Ford II Professor of Molecular, Cellular and Developmental Biology, has transformed our understanding of RNA. Far from playing second fiddle to proteins in cellular machinery, Breaker has found, RNA can play an array of exotic biochemical roles—and may have even been in charge of cellular functions during the dawn of evolution. Breaker’s extensive contributions to our understanding of RNA biology have now garnered him a new honor: On April 30, he was elected to the National Academy of Sciences (NAS), a body representing the nation’s most prominent and productive researchers.
“Ron has always done outstanding science,” says Robert J. Alpern, M.D., dean and Ensign Professor of Medicine. “He’s a pioneer in defining new RNA functions within the cell.”
Science had long held that RNA simply carries information between DNA and protein-manufacturing ribosomes. Breaker, also professor of molecular biophysics and biochemistry, suspected early on that nucleic acids like RNA might be capable of more than we gave them credit for.
In 1998 Breaker opened a new era of molecular biology when he synthesized the first RNA sequences that work as molecular switches. Soon afterward, he found the first such structures in nature, where they respond to metabolites and help determine which genes will be expressed. Some of these so-called “riboswitches” behave like enzymes, while others help bacteria process vitamins or even fend off fluoride—a great surprise, given that fluoride was not previously known to play much of a role in biological systems.
RNA may also behave like an antibody or a complex machine. One RNA “machine” Breaker’s lab discovered demands the presence of two specific chemical signals before it removes itself from a messenger RNA; another unusual RNA is essential for cells to tolerate high doses of alcohol. While organisms today mostly rely on proteins to do such things, some still use RNA. Breaker’s research suggests this may be a holdover from billions of years ago, before DNA existed, when RNA was the dominant machinery inside cells. If true, this notion would help clarify how life could have arisen without proteins, which require DNA instructions to build.
Breaker has also co-founded two biotech startups, Archemix and BioRelix, to explore RNA’s therapeutic and diagnostic capabilities, including novel antibiotics that target bacterial riboswitches.
Breaker earned his B.S. at the University of Wisconsin−Stevens Point, and his Ph.D. at Purdue University. As a postdoctoral fellow at the Scripps Research Institute, he helped develop methods of driving evolution in the lab to find RNA enzymes. It was there that he and his colleagues created the first enzymes made of DNA.
A Howard Hughes Medical Institute investigator, Breaker has received fellowships from the Arnold and Mabel Beckman Foundation, the David and Lucile Packard Foundation, and the Hellman Family Trust, and has won the Arthur Greer Memorial Prize, the Eli Lilly Award in Microbiology, and the Molecular Biology Award from the NAS. He was named a fellow of the American Association for the Advancement of Science in 2004.
The 105 new members and foreign affiliates named to the NAS this year include two other Yale faculty members: Xing-Wang Deng, Ph.D., Daniel C. Eaton Professor of Plant Biology in the department of molecular, cellular, and developmental biology; and David R. Mayhew, Ph.D., Sterling Professor of Political Science. All three will be inducted into the Academy during its April 2014 meeting in Washington, D.C.