An RNA molecule of about 45 nucleotides can copy itself into a complementary template when exposed to freezing temperatures and the right molecular building blocks.C. Bickel/Science
Today RNA may seem overshadowed by its glamorous cousin DNA, but many scientists think RNA molecules were the star players in the origin of life. By both storing genetic information and copying themselves, they might have touched off the march of evolution that produced increasingly complex life forms. So far, researchers haven’t found RNAs that can replicate themselves, a key feature of living things. But they now have something close. In a paper published online today in Science, researchers report creating RNAs that can generate a sort of mirror image of themselves and use that template to generate the original. A single RNA can’t complete the full cycle, but researchers say the advance gives a big boost to the idea that RNA was evolution’s first mover. “This is good stuff,” says Gerald Joyce, a chemist at the Salk Institute for Biological Studies and one of the pioneers of the “RNA world” hypothesis. He and others were drawn to RNA because even today, the molecule performs two functions vital for living things. It encodes genetic information in its sequence of chemical building blocks, called nucleotide bases. And the stable 3D structures into which it folds can carry out a second essential job: acting as catalysts to promote vital chemical reactions without being used up in the process. To many researchers, that dual role made RNAs a candidate for the kick-starter of life, able to both encode its own makeup and catalyze its own reproduction.
In 1993, after creating and testing libraries of trillions of different RNAs, researchers led by Jack Szostak, now at the University of Chicago, and David Bartel, now at the Massachusetts Institute of Technology, found ones that could perform some of the necessary functions. And in 2009, Joyce and his colleagues isolated two different RNAs that could synthesize each other. They could not duplicate themselves, however, and at 150 to 200 bases or more, they were too large to have arisen spontaneously from the compounds on early Earth. “They can’t come out of the [primordial] soup,” Joyce says. And at that size, they would likely degrade before they could be fully synthesized. The new versions, by contrast, are only about one-third the size, making their spontaneous appearance at least conceivable. “That’s a big innovation,” Joyce says. To minimize degradation, biochemists Edoardo Gianni and Philipp Holliger and their University of Cambridge team ran their experiments under freezing conditions. They suspected the low temperature would not only slow reactions that degrade RNA, but also aid the RNA-copying process. As water begins to freeze, it forces other compounds out of the growing ice crystals, concentrating nucleotides, salts, and other key building blocks of RNA synthesis in tiny solution-filled channels. The channels also have lower concentrations of liquid water, which speeds RNA degradation, Holliger explains.
When RNAs are in the freezing solution with a mixture of single nucleotides, most of the RNAs remain folded—the form they must assume to serve as catalysts. But to act as a template for copying, RNA molecules must be unfolded. Earlier reports suggested an approach: Introduce triplets of fused nucleotides that can help hold a template RNA strand in its open conformation. After experimenting with some 1 trillion different random RNA sequences in a freezing mixture, the team found that including both single bases and triplets allowed some RNA strands to fold up and act like catalysts, while others remain open for copying. The team found three RNAs, each about 45 bases long, that were able to copy themselves into complementary templates. The RNAs could also take the next step, starting with the templates and re-creating the originals. There’s no evidence yet that a single RNA can carry out both reactions, cycling between synthesizing its complement and then using that to synthesize itself. And the freezing temperatures meant it took some 72 days to synthesize new RNA strands. But life might have started in the cold: Many origin of life researchers believe Earth’s natural freeze-thaw cycles may have helped concentrate life’s building blocks. “The next challenge is to see if this or a similar system can be made sufficiently efficient to actually see repeated cycles of replication,” Szostak says. If that happens, RNA could leap from being a possible to a probable start to life.
doi: 10.1126/science.zddu0t3 출처 : Boosting origin of life theory, RNA comes close to copying itself | Science | AAAS | 
