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Researchers discover critical detail of cellular defense against genetic mistakes
Date:4/17/2008

ess such that it catches more genetic errors in some cases, or leaves more templates for helpful proteins in place in others, based on the disease at hand. To do so will require a highly detailed knowledge of the NMD pathway.

The current results uncover a critical and previously unappreciated step during the natural process that finds flaws in mRNAs, said Lynne E. Maquat, Ph.D., J. Lowell Orbison Endowed Chair and professor of Biochemistry & Biophysics at University of Rochester Medical Center, director of the University of Rochester Center for RNA Biology and lead author of the Cell piece. This work has important implications for our understanding of how one of the human cells most important activities, protein synthesis, undergoes quality control.

An Elegant Process Emerges

Over time, genes evolve to show changes in their makeup. Some changes, or mutations, have no impact, some provide advantages making organisms more likely to survive, and others cause disease. One frequently occurring, damaging class of mutation is the inclusion of premature stop reading signals (stop codons) within mRNAs. Called nonsense mutations, they order the process to stop reading part way through the genetic instructions. Such mutations result in the building of incomplete, disabled proteins that sabotage natural processes by competing for spots usually held by their full-length counterparts, or by simply not working. Mutations of this type cause genetic syndromes and contribute to many diseases, including cancer. Since truncated proteins are potentially hazardous, the NMD pathway has evolved to eliminate the mRNAs that encode them.

From studying genetic diseases, Maquat theorized seven years ago that there must be two types of translation, the process by which instructions encoded in mRNAs are read during protein building. An early pioneer round checks all newly built mRNAs for errors, and initiates NMD when errors are detected. Subsequent
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
University of Rochester Medical Center
Source:Eurekalert

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