RNA folding process reveals new twist.

The way RNA strands fold into their three-dimensional structures might not be as straightforward as researchers think, according to a new study.

Ignacio Tinoco Jr. and Ming Wu of the University of California, Berkeley have found that RNA molecules rearrange their internal structures as they fold into their final shape. The finding adds another layer of complexity to the already difficult problem of predicting how a strand of RNA will fold.

Scientists commonly believe that RNA folds in a stepwise process directed by interactions between the four bases, or molecular units, that constitute it: Guanine usually bonds with cytosine, and adenine with uracil.

When an RNA strand folds upon itself, base pairs near each other link up to create loops, twists, and kinks, features known as RNA's secondary structure. The strand then bends into its final three-dimensional shape, or tertiary structure, by simply forming bonds between bases left unpaired after the initial folding.

Tinoco and Wu examined a fragment of a ribozyme, a length of RNA that catalyzes biochemical reactions (SN: 7/22/95, p. 53). They determined the structure of the fragment, obtained from a microorganism called Tetrahymena thermophila, in solutions with and without magnesium ions, which normally stabilize the ribozyme's three-dimensional structure.

"By leaving out magnesium, you're just looking at the secondary structure," Tinoco explains. "When you add magnesium, [the RNA] goes into its tertiary folding."

The researchers found that, contrary to current belief, the transition between the secondary and tertiary structures involves rearrangement of some base-pair bonds, not just bonding by the unmatched bases. As the RNA folds into its tertiary structure, six of the original 19 base pairs break, and six new ones form.

"People thought that the base pairs were so stable that the tertiary structure wouldn't disrupt them," says Tinoco. "We've found that this is not always true." He and Wu report their findings in the Sept. 29 Proceedings of the National Academy of Sciences.

"Understanding RNA structure is key to understanding RNA function," says Scott K. Silverman of the University of Colorado at Boulder. Researchers use computers to help predict secondary structure from the base sequence, then make informed guesses about tertiary structure from those results. The new finding shows that "you might have to worry about what the tertiary structure looks like before you can draw the secondary structure correctly."