Fine-Tuning of Alanyl-tRNA Synthetase Quality Control Alleviates Global Dysregulation of the Proteome

Genes

Paul Kelly¹  Arundhati Kavoor¹  Michael Ibba¹ 

[1] The Ohio State University Molecular, Cellular and Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA;

关键词: aminoacyl-tRNA synthetases;    tRNA;    translational fidelity;   

DOI  :  10.3390/genes11101222

来源: DOAJ

【 摘 要 】

One integral step in the transition from a nucleic acid encoded-genome to functional proteins is the aminoacylation of tRNA molecules. To perform this activity, aminoacyl-tRNA synthetases (aaRSs) activate free amino acids in the cell forming an aminoacyl-adenylate before transferring the amino acid on to its cognate tRNA. These newly formed aminoacyl-tRNA (aa-tRNA) can then be used by the ribosome during mRNA decoding. In Escherichia coli, there are twenty aaRSs encoded in the genome, each of which corresponds to one of the twenty proteinogenic amino acids used in translation. Given the shared chemicophysical properties of many amino acids, aaRSs have evolved mechanisms to prevent erroneous aa-tRNA formation with non-cognate amino acid substrates. Of particular interest is the post-transfer proofreading activity of alanyl-tRNA synthetase (AlaRS) which prevents the accumulation of Ser-tRNA^Ala and Gly-tRNA^Ala in the cell. We have previously shown that defects in AlaRS proofreading of Ser-tRNA^Ala lead to global dysregulation of the E. coli proteome, subsequently causing defects in growth, motility, and antibiotic sensitivity. Here we report second-site AlaRS suppressor mutations that alleviate the aforementioned phenotypes, revealing previously uncharacterized residues within the AlaRS proofreading domain that function in quality control.

【 授权许可】

Unknown