Kleppe, AS., Bornberg-Bauer E.
Robustness by intrinsically disordered C-termini and translational readthrough
Nucleic Acids Research, 2018

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Abstract

During protein synthesis genetic instructions are passed
from DNA via mRNA to the ribosome to assemble a protein
chain. Occasionally, stop codons in the mRNA are bypassed
and translation continues into the untranslated region (3-
UTR). This process, called translational readthrough (TR),
yields a protein chain that becomes longer than would be
predicted from the DNA sequence alone. Protein sequences
vary in propensity for translational errors, which may yield
evolutionary constraints by limiting evolutionary paths. Here
we investigated TR in Saccharomyces cerevisiae by analysing
ribosome profiling data. We clustered proteins as either
prone or non-prone to TR, and conducted comparative
analyses. We find that a relatively high frequency (11%)
of genes undergo TR, including ribosomal subunit proteins.
Our main finding is that proteins undergoing TR are highly
expressed and have intrinsically disordered C-termini. We
suggest that highly expressed proteins may compensate
for the deleterious effects of TR by having intrinsically
disordered C-termini, which may provide conformational
flexibility but without distorting native function. Moreover,
we discuss whether minimizing deleterious effects of TR is
also enabling exploration of the phenotypic landscape of
protein isoforms.