RNA offers clue to life's start.

RNA Offers Clue to Life's Start

In answering the question of how life began, biologists can offer only plausible stories. One oft-described scenario highlights ribonucleic acids, or RNA, as the evolutionary link between life's chemical precursors and the first self-replicating cells. In contemporary cells, RNA carries genetic information and plays crucial roles in transforming genetic code into proteins.

To spawn the earliest living cells, RNA would have had to duplicate itself without the complex replicating enzymes and other chemicals used by cells. Researchers have found no such self-replicating molecules in nature.

Now, two molecular biologists claim their laboratory-modified RNA molecules can copy parts of themselves nearly unassisted. The researchers have yet to build an RNA molecule that can copy all of itself, but they say their work renders that goal realistic.

"If we can do this, it would show that self-replicating RNA could have been a major step in the evolution of life," says Jack W. Szostak of Massachusetts General Hospital in Boston. As a first experimental step, he and Jennifer A. Doudna have modified a type of RNA molecule--called a ribozyme -- found in protozoans and some other organisms. Ribozymes' normal role is to extract themselves from larger RNA molecules that contain them.

Other researchers have shown that the protozoan ribozyme can use a short segment on its own molecular body as a template for linking a limited group of short nucleotide sequences, or oligonucleotides. In a commentary accompanying the researchers' report in the June 15 NATURE, Thomas R. Cech of the University of Colorado in Boulder notes that the modified ribozyme overcomes the limitations in the length and variety of sequences it can link.

Using genetic engineering, Szostak and Doudna removed the ribozyme's internal template and showed that the new ribozyme could connect separate oligonucleotides aligned on specially designed, external templates. They also found that certain chemical additives, which may cause subtle changes in the ribozyme or templates, enable the ribozyme to connect oligonucleotides of nearly any sequence. In its best performance, the ribozyme stitched five oligonucleotides into a string of 45 nucleotides, Doudna says.

Says Szostak, "I think this is a big step toward building a real replicase"--a self-copying molecule that might have evolved into living cells. He and Doudna hope to develop their system so it copies the several-hundred-ribonucleotide string that would coil into a new ribozyme. "If we could make a replicase and then enclose it in an appropriate membrane, we would have primitive cells," Szostak says.

Molecular biologist Norman R. Pace of Indiana University in Bloomington says the modified ribozyme system could lead to new tools for researchers who paste nucleotides together into new molecules. As for the origin-of-life question, he says, Doudna and Szostak's work adds another chapter to a plausible story that no one can prove true.