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Scripps Research scientists solve long-standing mystery of protein 'quality control' mechanism
Date:9/12/2010

ps assembling the protein, and recruits factors that promote the protein's release into the cellular cytoplasm so the protein can go forth and perform its biological functions. When mRNA is accidentally missing a stop codon, however, the ribosome is like an auto manufacturing plant that can't get a car off the end of the linethe line stalls and production stops.

"In addition, these defective mRNA are problematic because they are translated into aberrant proteins," explained Joazeiro. "For these reasons, there are machineries in all living organismswhether bacteria or more complex eukaryotic organismsthat target and destroy both these non-stop messenger RNA and the resulting non-stop proteins."

For some 15 years, scientists have understood the mechanism that identifies and destroys these problematic non-stop proteins in bacteria. In these organisms, non-stop proteins are tagged by a marker known as tmRNA or ssrA, which then leads to their destruction.

In more complex eukaryotic organisms, which range from yeast to humans, though, the mechanism for identifying and eliminating such dangerous non-stop errors has remained a mysteryuntil now.

A Fresh Approach

Previously, scientists had failed to discover the missing quality control mechanism using a "homology" approach, in which they searched for molecules from eukaryotic organisms that looked like the bacterial tmRNA. Joazeiro and a postdoctoral fellow in his lab Mario Bengtson got to the mechanism by a different path.

In collaboration with Steve Kay's lab (now at the University of California, San Diego) the Joazeiro lab had discovered that a strain of mice carrying a mutation in a molecule known as Listerin experienced neurodegeneration. Because of recent studies from other labs and their own, the scientists suspected that Listerin could have a role in non-stop protein degradation.

To investigate, in the current study Joazeiro and Bengtson used the
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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