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April 20, 2007

Wild type gene expression regulation by the nonsense-mediated mRNA decay pathway

Dr. Audry Atkin

The nonsense-mediated mRNA decay (NMD) pathway is highly conserved.  It was originally studied for its role in ridding cells of mRNAs containing premature termination codons.  This function is important because it prevents the synthesis of potentially harmful truncated proteins.  However, in recent years it has become evident that this pathway also regulates expression of wild type genes.  Inhibition of nonsense-mediated mRNA decay in yeast, insects and humans changes the expression of 5-10% of the transcriptome.  This regulation is important because mutations that inactivate NMD cause a variety of phenotypes.  In yeast, these phenotypes include a growth defect on lactate, altered telomerase function and telomere length, and suppression of a missense mutation in CTF13.  We have developed a genome-wide strategy to identify regulatory networks that are affected by NMD and predict the physiological consequences of changes in expression of the network components.  Using this strategy, we have identified both transcription regulatory networks and novel mechanisms targeting mRNAs for NMD.  This strategy is significant because it allows us to classify the genes regulated by NMD into functionally related sets, an important step towards understanding the role NMD plays in normal yeast physiology.

URL for my website: http://bsweb.unl.edu/labs/atkin/index.html
URL for my departement website:  http://www.biosci.unl.edu/
URL for our Microbiology Initiative website:  http://www.microbiology.unl.edu/