Both in prokaryotic and eukaryotic genomes synonymous codons are unevenly used. Such differential usage of optimal or nonoptimal 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. In this work, using as model UreA, the Aspergillus nidulans urea transporter, we show that the synonymous mutation of a pair of nonoptimal codons coding for amino acids situated at the limit between the N-terminus and the first transmembrane segment are necessary for its proper biogenesis at 37ºC. This effect is less relevant at 25ºC. These codons presumably regulate translation rate in order to allow for the correct interaction of UreA-translating ribosomes with factors required for the targeting and/or folding of the protein, in a very early stage of the biosynthesis process. Whether this mechanism would affect other proteins, remains to be determined.
Raw data_figure 1.xlsx - Contains raw data of RSCUs
Raw data_Supplementary Figure S4b.xlsx