UB Scientists Report First Demonstration Of RNA 'Redox' Chemistry, Bolstering the Case for an RNA World

BUFFALO, N.Y. -- The first demonstration of reduction-oxidation, or redox, chemistry in RNA -- a critical missing link in the experimental evidence for an ancient RNA world -- was reported Sunday by University at Buffalo chemists in Nature Structural Biology online.

The publication confirms what until now has only been speculated: that RNA is capable of reduction-oxidation chemistry. The finding provides additional evidence that RNA may have played a critical role in the origin of life.

It also reveals a new discovery about RNA, opening up the possibility that whole new families of ribozymes capable of reduction-oxidation chemistry may exist.

"Reduction-oxidation reactions are essential for life to evolve because they are very important reactions in all metabolic cycles," explained Hiroaki Suga, Ph.D., UB associate professor of chemistry and co-author of the paper. "For a decade, people in the field have speculated that RNA must be capable of engaging in redox chemistry, but this is the first time it's been demonstrated."

The so-called RNA world is believed to be the evolutionary stage that predates present biological systems.

That hypothesis, Suga explained, is based on the premise that redox chemistry should be catalyzed by a ribozyme, an RNA catalyst, in an early life form, in the RNA world.

"Until now, the major evidence for that argument has been circumstantial," he said.

In this paper, the UB researchers describe the in vitro evolution of a ribozyme that oxidizes an alcohol using nicotinamide adenoside dinucleotide (NAD), an RNA cofactor, a substance essential to the modern reduction-oxidation reactions in protein enzymes.

According to Suga, it long has been suggested that RNA cofactors may be the molecular fossils of the RNA world, and that they still play a central role in reduction-oxidation chemistry in modern metabolic cycles. Thus, he said, it had been speculated that RNA molecules could have been the catalyst for reduction-oxidation chemistry before protein enzymes ever existed. To address whether reduction-oxidation reactions could be catalyzed by RNA molecules, Suga and his UB coauthors attempted to discover active redox ribozymes from a synthetic library of RNA sequences containing 100 trillion members.

"We designed an experimental system that could efficiently fish out active RNA molecules that accelerated the oxidation of alcohol," said Suga.

The ribozyme they isolated catalyzed the reduction-oxidation reaction of an alcohol molecule at least 7 orders of magnitude faster than would have been possible without it.

Suga's co-authors on the paper are Shinya Tsukiji, Ph.D., a post-doctoral fellow, and Swetansu B. Pattnaik, a doctoral candidate in the Department of Chemistry, both in the UB College of Arts and Sciences.

The research was funded by the National Science Foundation.