Evolving RNA with enzyme-like action.

In modern organisms, RNA molecules convey genetic information from DNA to the cellular machinery that churns out proteins. Some even work like enzymes, catalyzing reactions.

But a few researchers think RNA once played a much broader role, serving as a key component in the earliest life forms. That ancient RNA would have needed the ability to perform the tasks of many modern proteins, such as binding to an energy-transfer molecule called adenosine triphosphate (ATP). Yet through the millennia, RNA somehow lost these abilities.

To turn back the clock, two molecular biologists have harnessed a technique called molecular evolution (SN: 8/7/93, p.90). Working at Harvard Medical School in Boston, Mandana Sassanfar and Jack W. Szostak first generated 100 trillion different RNA molecules, each with 169 nucleotide building blocks. They then filtered these molecules through a gel containing ATP, in the hope of catching any RNA capable of linking to ATP. Next they poured a solution containing ATP through the used filter, this time hoping to wash off ATP-bound RNA that preferred to link to water-borne ATP. The researchers made many copies of whatever RNA molecules washed out and repeated that procedure until they finally had enough ATP-binding RNA to work with.

They determined the nucleotide sequences of the 39 kinds of RNA molecules that had bound to ATP. It turned out that those 39 kinds represented just 17 different sequences of nucleotides. These sequences all shared a region of 11 nucleotides, seven of which were exactly alike and four of which were similar, says Szostak. So he and Sassanfar made a new 40-nucleotide RNA containing this sequence and discovered that it also bound well to ATP. It seems that part of the RNA molecule becomes double stranded, with the 11 nucleotides forming a loop sticking out of one side, they report in the Aug. 5 Nature.

The researchers plan to incorporate this short RNA into sequences of a new set of RNA molecules and test those molecules for their ability to spur chemical reactions akin to those catalyzed by modern enzymes, Szostak says.