Unique Factors Surrounding Cell Stress
Proper regulation of gene expression is critical for the function of all cells, and the final stage of gene expression is the production of proteins. When this process—called protein synthesis or mRNA translation—is performed incorrectly, a variety of diseases can result, including diabetes and cancer.
Shu-Bing Qian, Nutritional Sciences, is working to uncover a novel mode of mRNA translational regulation during cell stress. This involves sugar modification of translational factors, what Qian calls the sweet regulation of stress response.
Under normal conditions in the cell, the translation machinery is recruited to the mRNA by a number of factors, one of which is a cap structure at the end of the mRNA. When the cell is under stress, for many proteins, the cap mechanism is shut down, and the production of proteins needed by the stressed cell is initiated without caps. The mechanism by which this cap-independent translation is initiated has been a long-standing question in the field of translational control. Qian’s group is investigating how the addition of a sugar called O-GlcNAc to a protein that initiates translation, eIF4G1, enables this cap-independent process. They are also looking at how the addition of these sugars interacts with the methylation of mRNA—how the cell remodels the conditions pre-synthesis to respond to stress and survive.
Qian’s studies will open new avenues of research in the field of mRNA translation, and the mechanistic insights will provide paradigms for better understanding of translational control in cellular homeostasis and stress adaptation.
NIH Award Number: 1R01GM122814-01