Atomic snapshot shows how RNA ruled

NORTHWESTERN (US) — Using powerful X-rays, researchers have produced an atomic picture of how ribonucleic acid (RNA) molecules interacted in the ancient world.

It is a rare glimpse of the transition from a time when RNA reigned supreme to the present, where proteins carry out the processes essential to life.

The images are the first to show the atomic details of how ribonuclease P (RNase P) recognizes, binds, and cleaves transfer RNA (tRNA). The researchers used X-rays produced by the Advanced Photon Source at Argonne National Laboratory to obtain the images from crystals formed by these two RNA molecules.

The result is a snapshot of one of the most complex models of a catalytic RNA and its target. Details of the structure are published by the journal Nature.

“RNA is an ancient molecule, but it is pretty sophisticated,” says study leader Alfonso Mondragón, professor of molecular biosciences at Northwestern University. “Our crystal structure shows that it has many of the properties we ascribe to modern molecules. RNA is a catalyst that has much of the versatility and complexity of modern-day proteins.”

For billions of years and still to this day, the function of RNase P—found in nearly all organisms, from bacteria to humans—has been to cleave transfer tRNA. If the tRNA is not cleaved, it is not useful to the cell.

“We knew this important chemistry happened, that RNA acts as a catalyst, but we didn’t know exactly how until now,” Mondragón says. “We now have a better understanding of how RNA works.”

RNase P is formed by a large RNA core plus a small protein, illustrating the evolutionary shift from an RNA world toward a protein-dominated world. The protein helps recognize the tRNA, but most of the recognition occurs through RNA-RNA interactions involving shape complementarity and also base pairing.

The structure shows that once RNase P recognizes tRNA, it docks and, assisted by metal ions, cuts one chemical bond. This matures the tRNA, producing a smaller RNA molecule that now can contribute to fundamental processes in the cell.

The RNA-based enzyme does this over and over, cutting each tRNA in exactly the same place every time.

“The discovery nearly 30 years ago that RNA molecules can have a catalytic function raised the idea that maybe RNA was the first molecule,” Mondragón says. “Our work reinforces this notion of the existence of an RNA world when life first began.”

Researchers from the University of Chicago coauthored the study, which was supported by the National Institutes of Health.

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