Abstract
In both prokaryotic and eukaryotic genomes, synonymous codons are unevenly used. Such differential usage of optimal or non-optimal codons has been suggested to play a role in the control of translation initiation and elongation, as well as at the level of transcription and mRNA stability. In the case of membrane proteins, codon usage has been proposed to assist in the establishment of a pause necessary for the correct targeting of the nascent chains to the translocon. By using as a model UreA, the Aspergillus nidulans urea transporter, we revealed that a pair of non-optimal codons encoding amino acids situated at the boundary between the N-terminus and the first transmembrane segment are necessary for proper biogenesis of the protein at 37°C. These codons presumably regulate the translation rate in a previously undescribed fashion, possibly contributing to the correct interaction of ureA-translating ribosome-nascent chain complexes with the signal recognition particle and/or other factors, while the polypeptide has not yet emerged from the ribosomal tunnel. Our results suggest that the presence of the pair of non-optimal codons would not be functionally important in all cellular conditions. Whether this mechanism would affect other proteins remains to be determined.
Highlights
Most amino acids are encoded by more than one codon, each of which is usually used with unequal frequencies across the genomes of different organisms or even across a single gene, a phenomenon known as ‘codon usage bias’ [1,2]
We identified a pair of non-optimal, conserved codons coding for amino acids localized just at the boundary between the N-terminus of the protein and the predicted first helical transmembrane segment (TMS), whose optimization leads to a deficiency in UreA synthesis at the optimal growth temperature of 37°C, while at 25°C, the defect becomes much less severe
The relative synonymous codon usage (RSCU) is the ratio of the observed frequency of synonymous codons in a group of genes to the expected frequency, if all the codons coding for the same amino acid were used
Summary
Most amino acids are encoded by more than one codon, each of which is usually used with unequal frequencies across the genomes of different organisms or even across a single gene, a phenomenon known as ‘codon usage bias’ [1,2]. A close positive correlation has been established between gene expression levels and the frequencies of usage of certain codons, which usually match the most abundant transfer RNAs (tRNAs), this correlation being attributed to natural selection leading to fast and accurate translation [5,6,7,8,9,10]. Translation rate control, in turn, has been related to the establishment of proper folding patterns, and functionality [15,16,17,18,19,20,21,22,23,24,25]
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