Step Closer to RNA World

In life as we know it, proteins are the workhorses of the cell, and the recipes on how to produce them are stored in DNA and RNA. But before the first cells arose on Earth, scientists believe, the world was awash in RNA molecules that behaved almost as if they were alive, catalyzing reactions and replicating themselves. Indeed, RNAs with such talents, called ribozymes, exist today. Scientists, however, have been hard-pressed to explain how life might have made the transition from a primordial "RNA world" to one in which proteins do the heavy lifting of life. Findings in this month's Nature Structural Biology make such a transition a bit more plausible, by showcasing a new talent for RNA: the ability to attach an amino acid to another RNA molecule, a crucial step in making proteins.

As part of the cell's protein-making machinery, proteins called amino-acyl tRNA synthetases add amino acids to molecules of transfer RNA (tRNA). Those tRNA molecules then line up along a messenger RNA template--a copy of a gene stored in a chromosome--and each of their attached amino acids are stitched together, forming a new protein.

Biochemist Hiroaki Suga of the State University of New York, Buffalo, and his colleagues wondered if they might be able to find ribozymes--rather than proteins--that could attach an amino acid to a tRNA, in theory filling one of the gaps between the RNA world and the world of proteins. The team ran a number of test tube evolution experiments, in which they let RNA sequences mutate and change, but only allowed those that met certain specifications to replicate. Eventually, they generated an RNA sequence that can bind to an activated glutamine and correctly attach the amino acid to its tRNA, precisely like proteins do in cells.

Other scientists have been able to produce ribozymes that can transfer amino acid to other RNA molecules, but the latest work is "the first time someone has put an amino acid onto a tRNA in the right place," says biochemist Paul Schimmel of The Scripps Research Institute in La Jolla, California. He notes that the reaction is inefficient: Less than 5% of the tRNA in the experiment received a glutamine. But the work shows how RNA molecules might have helped drive evolution toward proteins, he says: As more and more amino acids were attached to ribozymes, the RNA part of the molecules gradually became superfluous.