Abstract
As the central dogma of molecular biology, genetic information flows from DNA through transcription into RNA followed by translation of the message into protein by transfer RNAs (tRNAs). However, mRNA translation is not always perfect, and errors in the amino acid composition may occur. Mistranslation is generally well tolerated, but once it reaches superphysiological levels, it can give rise to a plethora of diseases. The key causes of mistranslation are errors in translational decoding of the codons in mRNA. Such errors mainly derive from tRNA misdecoding and misacylation, especially when certain codon-paired tRNA species are missing. Substantial progress has recently been made with respect to the mechanistic basis of erroneous mRNA decoding as well as the resulting consequences for physiology and pathology. Here, we aim to review this progress with emphasis on viral evolution and cancer development.
Highlights
In all living organisms, DNA is transcribed into RNA, and RNA is translated into protein
The latter process is executed by the ribosome, which constitutes the translation machinery that produces the cellular proteome by decoding mRNAs
Experiments employing misacylated aminoacyl-transfer RNAs (tRNAs) show that up to 10% of overall mistranslation in E. coli does not compromise physiology of this organism and is even compatible with bacterial proliferation [41]. aminoacyl-tRNA synthetases (aaRSs) of mycoplasma with mutations in the editing domain provoke misacylation tRNAs with highly similar amino acids that contribute to antigen diversity as to escape host immune defenses [49]
Summary
MRNA translation is not always perfect, and errors in the amino acid composition may occur. The key causes of mistranslation are errors in translational decoding of the codons in mRNA. Such errors mainly derive from tRNA misdecoding and misacylation, especially when certain codon-paired tRNA species are missing. Substantial progress has recently been made with respect to the mechanistic basis of erroneous mRNA decoding as well as the resulting consequences for physiology and pathology. We aim to review this progress with emphasis on viral evolution and cancer development
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