| Popis: |
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. |
