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Full-Text Articles in Biochemistry
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 …
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 …
Determining Whether The Nature Of The Amino Acid Substitution Or The Extent Of Mistranslation Affects The Impact Of Mistranslating Trnas In Saccharomyces Cerevisiae., Yanrui Zhu
Electronic Thesis and Dissertation Repository
Mistranslation occurs when an mRNA sequence is improperly decoded. Mistranslation can destabilize the proteome thus having a detrimental impact on the cell. tRNA variants with altered charging or decoding capabilities can increase mistranslation. Four mistranslating tRNAs were evaluated in yeast cells for their effect on growth, heat shock response, genetic interactions and cell morphology. Three of the tRNAs mistranslate at similar frequency, allowing for direct comparison of different amino acid substitutions. Each variant had distinct phenotypic consequences. Two of the tRNAs cause the same type of amino acid substitution but to different extents. The tRNA with the higher mistranslation frequency …