Sequence–structure relationships in yeast mRNAs

Abstract

It is generally accepted that functionally important RNA structure is more conserved than sequence due to compensatory mutations that may alter the sequence without disrupting the structure. For small RNA molecules sequence–structure relationships are relatively well understood. However, structural bioinformatics of mRNAs is still in its infancy due to a virtual absence of experimental data. This report presents the first quantitative assessment of sequence–structure divergence in the coding regions of mRNA molecules based on recently published transcriptome-wide experimental determination of their base paring patterns. Structural resemblance in paralogous mRNA pairs quickly drops as sequence identity decreases from 100% to 85–90%. Structures of mRNAs sharing sequence identity below roughly 85% are essentially uncorrelated. This outcome is in dramatic contrast to small functional non-coding RNAs where sequence and structure divergence are correlated at very low levels of sequence similarity. The fact that very similar mRNA sequences can have vastly different secondary structures may imply that the particular global shape of base paired elements in coding regions does not play a major role in modulating gene expression and translation efficiency. Apparently, the need to maintain stable three-dimensional structures of encoded proteins places a much higher evolutionary pressure on mRNA sequences than on their RNA structures.