Protein Synthesis and the Stress Response

Accuracy of protein synthesis is critical for life since a high degree of fidelity of the translation of the genetic information is required to accomplish the needs of the cellular functions as well as to preserve the variability developed by evolution. More than one hundred macromolecules are involved in this process even in the simplest organisms, including ribosomal proteins, translation factors, aminoacyl-tRNA synthetases as well as ribosomal and transfer RNAs (being rRNAs near 80% of total cellular RNAs in bacteria). Accuracy of translation of the genetic information is accomplished at different levels, being one of the most relevant the specific interaction of the aminoacyl-tRNA synthetases with their substrates, tRNA and amino acids. Either specific molecular interactions that avoid the miss-incorporation of amino acids or the hydrolysis of wrong aminoacyl-tRNAs represent strategies utilized by the aminoacyl-tRNA synthetases to reduce the formation of missacilated tRNAs. Additionally, the discrimination by the elongation factor Tu (EF-Tu) against miss-acylated aminoacyl-tRNAs over correctly acylated increases the accuracy of incorporation of the proper aminoacyl-tRNAs to the ribosome. The accurate decodification of the mRNA by the incorporation of the aminoacyl-tRNA with the correct anticodon ensures the fidelity of translation of the genetic information. The consequence of these discriminatory events led to an accuracy of translation of the genetic information to as low as 10-4 errors per amino acid incorporated. However, certain level of inaccuracy might be tolerated, even might be beneficial to the cells under certain physiological and environmental conditions.