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Tiny RNA Molecule Has Big Implications for Origin of Life

The smallest RNA enzyme ever known to perform a cellular chemical reaction has been described in a paper published online on February 22 in PNAS. Scientists at the University of Colorado at Boulder (UCB) have synthesized an extremely small RNA molecule that can catalyze a key reaction needed to synthesize proteins, the building blocks of life. The findings could be a substantial step toward understanding "the very origin of earthly life," contended graduate student and first author Rebecca Turk. The research team, led by Dr. Michael Yarus, focused on a ribozyme—a form of RNA that can catalyze chemical reactions—that was made up of only five nucleotides. Because proteins are complex, one vexing question has been where the first proteins came from, said Dr. Tom Blumenthal, chairman of the Molecular, Cellular, and Developmental Biology (MCDB) department at UCB, who was not involved in the research. "It now appears that the first catalytic macromolecules could have been RNA molecules, since they are somewhat simpler, were likely to exist early in the formation of the first life forms, and are capable of catalyzing chemical reactions without proteins being present," he said. "In this paper, the Yarus group has made the amazing discovery that even an extremely tiny RNA can by itself catalyze a key reaction that would be needed to synthesize proteins," said Dr. Blumenthal. “Nobody expected an RNA molecule this small and simple to be able to do such a complicated thing as that." The finding adds weight to the "RNA World" hypothesis, which proposes that life on Earth evolved from early forms of RNA. "Mike Yarus has been one of the strongest proponents of this idea, and his lab has provided some of the strongest evidence for it over the past two decades," Dr. Blumenthal said. Dr. Yarus noted that the RNA World hypothesis has been complicated by the fact that RNA molecules are hard to make. "This work shows that RNA enzymes could have been far smaller, and therefore far easier to make, under primitive conditions, than anyone has expected." "Dr. Yarus has brought an innovative approach to bear on the key question of how complex processes originated," said Dr. Michael Bender, a biologist who oversees protein synthesis grants at the NIH’s National Institute of General Medical Sciences. "By showing that a tiny segment of RNA can perform a key step of protein synthesis, this study has provided evidence that fundamental, protein-mediated cellular processes may have arisen from RNA-based mechanisms." [Press release] [PNAS article]