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Probing The Genetic Code With Leucine Trna Variants, Peter Anderson Hall
Probing The Genetic Code With Leucine Trna Variants, Peter Anderson Hall
Electronic Thesis and Dissertation Repository
Mistranslation is an error in protein synthesis whereby the amino acids specified by the genetic code are misplaced by others in the growing polypeptide chain. The anticodon of tRNALeu can be altered allowing for the misincorporation of leucine at non-leucine codons. Observing the effect of tRNALeu variants on the viability of yeast and mammalian cells will provide information on their ability to cause mistranslation and potential relationship to genetic diseases. To explore this, a random pool of tRNALeu anticodonvariants was expressed in Saccharomyces cerevisiae. Furthermore, three mutant tRNALeu already sequenced from humans were expressed in …
Perseverance Of Protein Homeostasis Despite Mistranslation, Farah Hasan
Perseverance Of Protein Homeostasis Despite Mistranslation, Farah Hasan
Electronic Thesis and Dissertation Repository
Transfer RNAs (tRNAs) are essential for protein synthesis and translation fidelity. Some human tRNA variants may cause amino acid misincorporation: tRNAGly variants (tRNAGlyCCC, tRNAGlyGCC) have mutations that generate an alanine tRNA identity element (G3:U70), likely causing mis-aminoacylation of glycine tRNAs with alanine, while the tRNAAlaAGC G35C (tRNAAlaACC) variant may function similarly to mis-incorporate Ala at Gly codons by generating a Gly anticodon. I propose that these mistranslating tRNAs will disrupt protein homeostasis in mammalian cells. Although the tRNAGly and tRNAAla variants did not affect protein synthesis …
Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib
Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib
Undergraduate Student Research Internships Conference
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 …
Illuminating Transfer Rna Variants As Genetic Modifiers In Models Of Human Disease, Jeremy T. Lant
Illuminating Transfer Rna Variants As Genetic Modifiers In Models Of Human Disease, Jeremy T. Lant
Electronic Thesis and Dissertation Repository
Transfer RNAs (tRNAs) physically link the genetic code to an amino acid sequence, by recruiting amino acids to three-nucleotide codons in messenger RNAs. To ensure that the genetic code is translated as intended, tRNAs must be accurately aminoacylated and faithfully recognize codons in the ribosome during protein synthesis. Given the critical function of tRNAs, it has often been assumed that mutations in human tRNA genes would be either lethal to cells or not significantly impair tRNA function. My goal was to rigorously test this assumption in mammalian cell models, prompted by the recent discovery of unprecedented variation in human tRNA …