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Scripps Research scientists observe human neurodegenerative disorder in fruit flies
Date:6/24/2009

ponding single-stranded piece of messenger RNA. Then an enzyme called the ribosome uses the mRNA as a template to make a protein by reading out its genetic sequence and then translating it into a string of amino acids. That's where the tRNA synthetases are needed.

When building new proteins, ribosomes rely on a set of molecules called transfer RNAs (tRNAs) to supply them with the amino acids they need to construct the proteins. The tRNA synthetases are needed to attach amino acids to the tRNAs.

Sound complicated? It is. But the action of tRNA synthetases is also so essential that every creature on the planet has these molecules, which probably evolved very early on as life first emerged on Earth.

"These proteins are among the first to appear in the planet," says Schimmel, who led the current research effort. "All cells need them to grow, divide, and survive."

When mutations in tyrosyl-tRNA synthetase were linked to Charcot-Marie-Tooth disease a few years ago, scientists debated whether problems arose because the mutations interfered with tRNA synthetase's normal function, helping to express genes into proteins, or whether they arose because the mutations interfered with some other unknown function.

Schimmel had been studying this type of molecule for many years and had already discovered novel functions that had evolved over time in some tRNA synthetases, including this one. He reckoned that, if one could first show that a CMT-causing mutant synthetase was active for protein synthesis, then recreating the same disease in another organism (by putting the same mutations in the other organism's analogous gene) would demonstrate that a novel function was at play.

This is exactly what he and his scientific collaborators did. After showing that the disease was not caused by a defect in the synthetase's activity for protein synthesis, the researchers created the same mutations to the equivalent protein in the fruit fl
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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