Quality control despite mistranslation caused by an ambiguous genetic code
| Autor: | Sotiria Palioura, Benfang Ruan, Robert A. LaRossa, Sunil Kochhar, Laure Marvin-Guy, Dieter Söll, Jeffrey Sabina |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Genetics
Aminoacyl-tRNA Multidisciplinary Mutation Missense Context (language use) Translation (biology) Biology Biological Sciences RNA Transfer Amino Acyl Genetic code medicine.disease_cause Mass Spectrometry chemistry.chemical_compound chemistry Mutant protein Genetic Code Protein Biosynthesis medicine Protein biosynthesis Escherichia coli Protein quality Heat-Shock Response |
| Popis: | A high level of accuracy during protein synthesis is considered essential for life. Aminoacyl-tRNA synthetases (aaRSs) translate the genetic code by ensuring the correct pairing of amino acids with their cognate tRNAs. Because some aaRSs also produce misacylated aminoacyl-tRNA (aa-tRNA) in vivo, we addressed the question of protein quality within the context of missense suppression by Cys-tRNA Pro , Ser-tRNA Thr , Glu-tRNA Gln , and Asp-tRNA Asn . Suppression of an active-site missense mutation leads to a mixture of inactive mutant protein (from translation with correctly acylated aa-tRNA) and active enzyme indistinguishable from the wild-type protein (from translation with misacylated aa-tRNA). Here, we provide genetic and biochemical evidence that under selective pressure, Escherichia coli not only tolerates the presence of misacylated aa-tRNA, but can even require it for growth. Furthermore, by using mass spectrometry of a reporter protein not subject to selection, we show that E. coli can survive the ambiguous genetic code imposed by misacylated aa-tRNA tolerating up to 10% of mismade protein. The editing function of aaRSs to hydrolyze misacylated aa-tRNA is not essential for survival, and the EF-Tu barrier against misacylated aa-tRNA is not absolute. Rather, E. coli copes with mistranslation by triggering the heat shock response that stimulates nonoptimized polypeptides to achieve a native conformation or to be degraded. In this way, E. coli ensures the presence of sufficient functional protein albeit at a considerable energetic cost. |
| Databáze: | OpenAIRE |
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