Abstract
A critical assumption of gene expression analysis is that mRNA abundances broadly correlate with protein abundance, but these two are often imperfectly correlated. Some of the discrepancy can be accounted for by two important mRNA features: codon usage and mRNA secondary structure. We present a new global factor, called mRNA:ncRNA avoidance, and provide evidence that avoidance increases translational efficiency. We also demonstrate a strong selection for the avoidance of stochastic mRNA:ncRNA interactions across prokaryotes, and that these have a greater impact on protein abundance than mRNA structure or codon usage. By generating synonymously variant green fluorescent protein (GFP) mRNAs with different potential for mRNA:ncRNA interactions, we demonstrate that GFP levels correlate well with interaction avoidance. Therefore, taking stochastic mRNA:ncRNA interactions into account enables precise modulation of protein abundance.
Highlights
It should in principle be possible to predict protein abundance from genomic data
By generating synonymously variant green fluorescent protein (GFP) messenger RNAs (mRNAs) that differ in their potential to interact with core ncRNAs, we demonstrate that GFP expression levels can be both predicted and controlled
To examine if avoidance of stochastic mRNA:ncRNA interactions is a feature of transcriptomes in bacteria and archaea, we estimated the strength of all possible intermolecular RNA interactions using a minimum free energy (MFE) model (Muckstein et al, 2006) using core ncRNAs and mRNAs
Summary
It should in principle be possible to predict protein abundance from genomic data. protein and mRNA levels are not strongly correlated (de Sousa Abreu et al, 2009; Vogel and Marcotte, 2012; Kwon et al, 2014; Maier et al, 2011; Lu et al, 2007; Taniguchi et al, 2010; Chen et al, 2016), which is a major barrier to precision bioengineering and quantification of protein levels. mRNA secondary structure (Pelletier and Sonenberg, 1987; Chamary and Hurst, 2005), codon usage (Ikemura, 1981; Sharp and Li, 1987; Andersson and Kurland, 1990), and mRNA (and protein) degradation rates (Maier et al, 2011) are commonly invoked to explain this discrepancy (Boel et al, 2016-21).
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