Scientists tinkering with a chemical now vital to life think they’ve recreated one of the central molecules that first gave rise to the chemistry of life.
Hiroaki Suga of the State University of New York at Buffalo and his coworkers from Buffalo and the University of Tokyo altered a type of RNA, or ribonucleic acid, the chemical that orchestrates protein making. The researchers found that their modified RNA could by itself perform functions that normally require the help of proteins. Their work, which appears in the April 2 EMBO Journal, supports the hypothesis of a prebiological “RNA world,” in which RNA molecules assembled and copied themselves, acting almost as independent living things.
The critical problem in pinning down the origin of life is, “When did the first structure that could both replicate itself and accumulate mutations evolve?” says molecular evolutionist Walter Gilbert of Harvard University. His 1986 article in Nature explored the idea of a world dominated by RNA and coined the term for it. “The RNA-world idea is an answer to the problem of when the first information began to copy itself and make more information,” he says.
There are other candidates for the first lifelike molecule, namely proteins and DNA. Suga contends, however, that RNA remains the most plausible candidate. “With the others you have the chicken-and-egg type of problem,” says Suga. DNA encodes instructions for making proteins but can’t build the protein molecules. Proteins can synthesize molecules—including proteins, DNA, and RNA—but only with instructions from other molecules.
Several types of RNA normally bridge these ability gaps by shuttling copies of DNA information to protein-making RNA molecules. One type of RNA molecule, called transfer RNA, binds to amino acids, the basic building blocks of proteins. Enzymes, which are a type of protein, catalyze this linkage. For years, researchers have known that some forms of RNA have enzymelike activity. Now, Suga and his colleagues have shown that RNA can even catalyze this linking of an amino acid to RNA.
“Showing that RNAs could accomplish this step, too, catalyzing the synthesis of proteins, is an important confirmation” of the RNA-world idea, says Michael J. Yarus, who studies RNA reactions at the University of Colorado in Boulder.
Suga and his coworkers applied a kind of test-tube evolution to unveil this new catalytic ability of RNA. First they selected from a pool of RNA molecules the very few that could bind to a modified version of phenylalanine, one of the 20 amino acids that make up proteins. Then they copied these RNA “winners” and repeated the process. After 14 such rounds, the researchers ended up with an RNA molecule tailor-made to bind to the amino acid.
In doing so, they isolated what Suga calls a biological fossil of the RNA world. These RNA molecules have an intriguing structural motif, absent in normal RNA, that recognizes an amino acid and chemically binds to it, forming a novel type of RNA enzyme, or ribozyme. The team has filed a patent on the ribozyme.
“People have conjectured that there would be a step in which RNA molecules played the role of proteins, attaching amino acids to the transfer RNA molecule. This paper shows that [RNA] could play that role,” says Gilbert.