Folding Patterns Offer Clues to RNA's Family Tree

The search for a hypothetical ancestor of some or all of the types of RNA now known might be possible using a technique pioneered by scientists at MIT's Whitehead Institute, according to speakers at the APS March Meeting.

Just as DNA samples can be used to study the spread of humans to different parts of the world, as well as to study connections among various lineages among living organisms, so too there might be ways of studying the origins of RNA.

RNA is increasingly considered by scientists to be the most likely candidate for the origin of life. It starts out single-stranded, but can at many places along its length double over on itself to arrive at complicated, twisted shapes. Like DNA, it is found in abundance in living cells, but it has the advantage of being a two- pronged biomolecule. Not only can it carry genetic information, it can also fold into protein-like molecules that can catalyze important biochemical reactions.

At the APS meeting, numerous researchers discussed how the folding patterns of RNA molecules support the notion that RNA is connected to the origin of life, and may even explain why nature chose four letters for the genetic code. Also, RNA folding has supplied insights into other questions on how proteins fold into their final shapes.

MIT-Whitehead's Erik Schultes reported on an experiment in which a particular sequence of RNA bases could, by altering one base at a time, quickly take on the identity of either of two very different ribozymes (RNA molecules that can catalyze reactions).

Schultes compared this to transforming the word "cat" into the word "dog" through a sequence of single- letter mutations, each one of which resulted in a legitimate word: cat-cot-cog-dog.

Ranjan Mukhopadhyay reported that he and his colleagues at NEC Laboratories in New Jersey have found that a typical RNA sequence with its 4-base chemical code folds more predictably and stably than would hypothetical RNA sequences based on a two-base or six-base "alphabet."

In other theoretical work, Ralf Bundschuh of Ohio State University and Terence Hwa of University of California, San Diego, have shown that RNA could exhibit several different "phases," just as water can exist in the solid, gaseous or liquid forms.