Faculty
Department of Anatomy and Cell Biology
Supervisor Name
Patrick Lajoie, Martin Duennwald
Keywords
ALS, tRNA, mistranslation, protein, protein misfolding, heat shock response, Hsf1
Description
Translation, or the production of protein from an mRNA blueprint, is among the most fundamental processes to life as we know it. tRNAs are essential to accurate translation, as they decode the codons of mRNA and recruit corresponding amino acids. Variant tRNAs with anticodon mutations can decrease translational fidelity by recruiting the incorrect amino acid, an aberrant process known as mistranslation. When proteins are produced with incorrect amino acid sequences, they may misfold. The heat shock response functions to alleviate cellular stress caused by misfolded proteins, either by refolding or targeting misfolded proteins for degradation. Hsf1 acts as a transcriptional regulator of the heat shock response in cells, and is therefore essential for the tolerance of misfolded proteins. We use molecular tools to simultaneously induce mistranslation and dysregulate the heat shock response through the expression of mistranslating serine tRNA variants and functional variants of Hsf1, respectively. Together, these tools allow us to investigate the complex relationship between mistranslation and the heat shock response. My research suggests that, while the heat shock response is important for tolerance of mistranslation, high levels of the heat shock response are maladaptive.
Acknowledgements
I would like to thank the USRI program for enabling me to engage in a summer research internship. I would also like to thank Dr. Martin Duennwald, Dr. Patrick Lajoie and Donovan McDonald for sponsoring my USRI award application and for supervising my research.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Document Type
Poster
Included in
Biochemistry Commons, Genetic Phenomena Commons, Medical Biochemistry Commons, Medical Cell Biology Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Neurobiology Commons, Molecular Biology Commons
Mistranslating tRNAs alter the Heat Shock Activation by Hsf1
Translation, or the production of protein from an mRNA blueprint, is among the most fundamental processes to life as we know it. tRNAs are essential to accurate translation, as they decode the codons of mRNA and recruit corresponding amino acids. Variant tRNAs with anticodon mutations can decrease translational fidelity by recruiting the incorrect amino acid, an aberrant process known as mistranslation. When proteins are produced with incorrect amino acid sequences, they may misfold. The heat shock response functions to alleviate cellular stress caused by misfolded proteins, either by refolding or targeting misfolded proteins for degradation. Hsf1 acts as a transcriptional regulator of the heat shock response in cells, and is therefore essential for the tolerance of misfolded proteins. We use molecular tools to simultaneously induce mistranslation and dysregulate the heat shock response through the expression of mistranslating serine tRNA variants and functional variants of Hsf1, respectively. Together, these tools allow us to investigate the complex relationship between mistranslation and the heat shock response. My research suggests that, while the heat shock response is important for tolerance of mistranslation, high levels of the heat shock response are maladaptive.