It is presumed that the levels of mRNA and protein should correlate relatively strongly however this correlation is often quite poor. Two main explanations have been invoked to explain this discrepancy, messenger RNA (mRNA) secondary structure and codon usage bias, however, these explanations only account for around 40% of the total variation in expression levels. More recently a new model has been proposed that explains more of the variation in mRNA and protein levels than either codon usage or mRNA secondary structure.

The mRNA: ncRNA avoidance model, presents evidence that non-specific interactions between non-coding RNAs (ncRNAs) and mRNAs significantly impact the discrepancy between mRNA and protein abundances. The model suggests that these crosstalk interactions between mRNAs and ncRNAs impact levels of mRNA translation, consequently genes that are highly-expressed demonstrate avoidance of such interactions.

Here I present a study that investigates how highly expressed mRNAs may have evolved to avoid unintentional interactions with the abundant ncRNAs in the cell. Synonymous variants of the araC gene of E. coli were designed for increased interaction with core ncRNAs. These alterations were predicted to lead to down regulation of the AraC protein and subsequently impact fitness. We hypothesised that evolution of avoidance could then be driven by creating a selective pressure for high expression of araC, such that the affinity of the designed araC mRNAs for ncRNAs would be lessened to increase translation levels. The findings here demonstrate that the alterations made to the araC variants, which are in line with the avoidance model, have an undetectable effect on fitness in E. coli. Furthering our understanding of how this phenomenon may have evolved has significant implications for the biology of RNA-RNA interaction.