Scientists discover new class of RNAs

CAMBRIDGE, Mass. — The last few years have been very good to RNA. Decades after Watson and Crick’s central dogma took biology by storm, RNA was considered little more than a link in a chain—no doubt a necessary link, but one that, by itself, had little to offer. But with the discoveries of RNA interference and microRNAs, this meager molecule has been catapulted to stardom as a major player in genomic activity.

As sequencing technology continues to ramp up, RNA influence appears more widespread by the month. Recently, a team of scientists in the lab of Whitehead Member and Howard Hughes Medical Institute Investigator David Bartel discovered an entirely new class of RNA molecules. Reporting in the journal Cell, the team describes identifying more than 5,000 of these new molecules, termed 21U-RNAs, in the C. elegans worm. These new RNAs are named after their distinctive features: Each molecule contains 21 chemical building blocks (or nucleotides), and each begins with the chemical uridine, represented by the letter U (the only RNA nucleotide not also found on DNA). In addition, each of the 5000 different 21U-RNA molecules come from one of two chromosomal regions. And while the 21Us themselves have diverse sequence patterns, the DNA sequences residing just outside those that give rise to each 21U are identical.

“Using the sequence pattern, we can predict where additional 21U-RNA genes might reside,” says Bartel. “Combining these predictions with the 5,000 that we experimentally identified, we suspect that there are more than 12,000 different 21U-RNA genes in the genome.” Because each gene typically produces a unique 21U-RNA, a very large diversity of molecules is made.

“There are so many 21U-RNA genes spread out over such a wide swathe of the genome, but they all share common requirements for expression and common structural features,” says Bartel-lab PhD student J. Graham Ruby, lead author on the paper.

Because of this, the researchers believe that even though they haven’t yet identified a particular function for these molecules, this uniform structure strongly indicates an important role.

MIT professor and Nobel Laureate Phillip Sharp, who was not part of the research team, supports this hypothesis. The fact that 21U-RNAs share this “common structure and origin suggests an important function,” he says. “It requires function to conserve specificity.”

This research was supported by the Prix Louis D from the Institut de France and a grant from the National Institutes of Health.

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Ruby, G. et al. “Large-Scale Sequencing Reveals 21U-RNAs and Additional MicroRNAs and Endogenous siRNAs in C. elegans.” Cell, December 15, 2006; Vol 127:1193-1207