Scientists reveal the structure of RNA that can leap around the genome.

The tertiary structure of the intron, with the active center of the molecule in red.

Not all RNA is content to inactively remain in linear genetic fragments. Some bits of RNA can break away, or self-splice, and invade other areas of RNA and DNA, driving the evolution of new genes. Now a group of scientists, led by HHMI investigator Anna Marie Pyle of Yale University, has determined the structure of one of these feisty stretches of nucleotides.

Unlike DNA—typically found in basic double helices—RNA frequently adopts intricate structures, folding back on itself, making loops and hairpins and globs. Predicting how any given bit of RNA will arrange itself is exceedingly difficult given the possibilities. And studying this type of mobile RNA—known as group II introns—presents its own problems because the RNA is often reluctant to jump when it's not inside a cell.

Therefore, Pyle and her colleagues first had to find one that would cooperate in a test tube. After screening group II introns from a number of organisms—the jumping RNA exists in almost all bacteria, and in some plants, fungi, and animals—the group identified an intron from a deep-sea bacterium that readily self-spliced in the laboratory.

They isolated the intron—once it had already hopped out of its spot in the genome but before it had barged into a new gene—and used x-ray crystallography to generate a detailed picture of its structure. The results appear in the April 4, 2008, issue of Science.

They found that the RNA folds into a globular shape, with the active parts of the molecule—needed for the splicing—nestled inside. These active parts, they noticed, bear striking similarity to substructures in the spliceosome—a complex of RNA and proteins that normally removes unneeded sections from a strand of RNA before it is used to code for a protein.

“I had high hopes that we would learn a lot from this molecule about the way RNA folds,” says Pyle. “And indeed, it really surprised us about the kind of structures that RNA can adapt. This was a treasure trove of structures.”

Photo: Kevin Keating / Pyle lab