A New Glimpse into the Evolution of the Code of Life

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Life is based on the ability of all living cells to convert the genetic information in DNA, into the specific sequences of amino acids that make up the proteins that are the cell's workhorses. The key reaction in this decoding process is the attachment of a particular amino acid to one end of a small RNA molecule known as a transfer RNA. The enzyme that catalyzes this amino acid-RNA attachment is the aminoacyl-tRNA synthetase.


UC Santa Barbara graduate student Annia Rodriguez worked with John Perona, professor in UCSB's Department of Chemistry and Biochemistry to decipher intramolecular communication within a large RNA-protein enzyme responsible for expressing the genetic code for the amino acid glutamine. Rodriguez performed experiments in which she removed portions of the aminoacyl-tRNA synthetase that interact with the anticodon stem of the transfer RNA, far from the part of the enzyme that binds the amino acid.

Using a biochemical approach known as rapid chemical quench kinetics, Rodriguez discovered that when she made these changes to the enzyme, the binding of the amino acid to the protein was strengthened, even though the amino acid binds far away from the positions where the changes were made.

"It is totally counterintuitive," said Perona. "Imagine if you had a car, and you took out a gear, and the car went faster. Why would you want that gear if it makes your car go slower?"

In all, Rodriguez found that separately removing seven different "gears" from a distant part of the molecule each caused the amino acid to bind more tightly to the aminoacyl-tRNA synthetase. Perona explained that this provides the first systematic analysis demonstrating long-range communication in an enzyme that depends on RNA for its function.

"So what we think is going on is that these enzyme-RNA interactions far from the amino acid binding site evolved together with the needs of the cell to respond to subtle cues from its environment – especially in terms of how much amino acid is available," said Perona. "It makes sense in terms of evolution."

The Daily Galaxi via University of California – Santa Barbara

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