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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 …
Site-Specific Effects Of Lysine Acetylation On Aminoacyl-Trna Synthetase, Hao Chen
Site-Specific Effects Of Lysine Acetylation On Aminoacyl-Trna Synthetase, Hao Chen
Graduate Theses and Dissertations
Aminoacyl-tRNA synthetases (AARSs) are an ancient and highly conserved family of enzymes which can catalyze a two-steps aminoacylation reaction to charge tRNAs with their cognate amino acids, thus playing crucial roles in ribosomal protein synthesis. Naturally, the accurate amino acids and tRNA recognition of these synthetases are essential to the fidelity of translation process. To assure the correct recognition, some of these synthetases have evolved with an editing function to help remove the mischarged tRNAs. In addition to these functions, AARSs are also involved in various biological processes ranging from transcription to translation. Currently, a series of proteomic studies have …
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 …
Functional Characterization Of Accessory Proteins And Novel Activities In Direct And Indirect Trna Aminoacylation, Udumbara Menike Rathnayake
Functional Characterization Of Accessory Proteins And Novel Activities In Direct And Indirect Trna Aminoacylation, Udumbara Menike Rathnayake
Wayne State University Dissertations
Indirect tRNA aminoacylation is essential for most bacteria and archaea, particularly when these species do not have genes encoding asparaginyl- and/or glutaminyl-tRNA synthetase (AsnRS and GlnRS). In the absence of AsnRS, the first step in Asn-tRNAAsn synthesis involves misacylation of tRNAAsn with aspartate to produce Asp-tRNAAsn; this reaction is catalyzed by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS). Subsequently, in bacteria, an amidotransferase called GatCAB converts Asp-tRNAAsn to Asn-tRNAAsn. An analogous, two-step processes exist to produce Gln-tRNAGln. In this case, a non-discriminating glutamyl-tRNA synthetase (ND-GluRS) misacylates tRNAGln to produce Glu-tRNAGln, which is then converted to Gln-tRNAGln by GatCAB. The central hub of …