Mathematical Biology Seminar Julie Hollien Biology Department, University of Utah Wednesday, April 29, 2009 3:05pm in LCB 215 mRNA degradation and how cells cope with stress Abstract: Proteins that are destined to be secreted from the cell are initially synthesized at the surface of the endoplasmic reticulum (ER) and processed within the lumen of the ER. In addition to folding and processing an enormous flux of secreted proteins, the ER must maintain a strict quality control system to ensure that potentially harmful, misfolded proteins do not traffic to the cell surface. Normally the cell maintains a balance between the load of incoming proteins and the capacity of the folding machinery within the ER. When this balance is disrupted (a situation referred to as ER stress), the cell initiates a broad transcriptional remodeling of the ER, by upregulating chaperones and many other genes associated with ER function. We have found that cells also respond to ER stress by rapidly degrading mRNAs associated with the ER membrane. This pathway has the potential both to immediately relieve the load on the ER (by destroying the templates for proteins that are processed in the ER) and to clear out translation and folding machinery to accommodate the influx of new chaperones and other ER-associated factors. We are currently working to understand the mechanism and specificity of this process, as well as developing new tools to look at mRNA degradation and regulation on a genome-wide scale.