Abstract
Bacterial mRNAs are organized into operons consisting of discrete open reading frames (ORFs) in a single polycistronic mRNA. Individual ORFs on the mRNA are differentially translated, with rates varying as much as 100-fold. The signals controlling differential translation are poorly understood. Our genome-wide mRNA secondary structure analysis indicated that operonic mRNAs are comprised of ORF-wide units of secondary structure that vary across ORF boundaries such that adjacent ORFs on the same mRNA molecule are structurally distinct. ORF translation rate is strongly correlated with its mRNA structure in vivo, and correlation persists, albeit in a reduced form, with its structure when translation is inhibited and with that of in vitro refolded mRNA. These data suggest that intrinsic ORF mRNA structure encodes a rough blueprint for translation efficiency. This structure is then amplified by translation, in a self-reinforcing loop, to provide the structure that ultimately specifies the translation of each ORF.
Highlights
Protein synthesis is the most energetically costly process in bacteria, consuming up to 50% of cellular energy
Structures determined from E. coli-adapted dimethyl sulfate (DMS)-seq are in excellent agreement with both the 16S rRNA crystal structure (Figure 1C) (Zhang et al, 2009), and a mutationally verified E. coli mRNA structure (Figure 1D) (Wikstrom et al, 1992)
We found that the degree of RNA secondary structure varied greatly between Open reading frames (ORFs): a small number are nearly as structured as rRNA, whereas some are close to the denatured state (Figure 1F)
Summary
Protein synthesis is the most energetically costly process in bacteria, consuming up to 50% of cellular energy. To optimize cellular efficiency, the rate of synthesis of each protein must be carefully controlled. The translation of each ORF in the operon is precisely tuned to cellular need. The rate of protein production (i.e. the translation efficiency) of adjacent ORFs on a single mRNA can vary by as much as 100-fold, and members of protein complexes encoded on a single mRNA are generally translated in proportion to their stoichiometry (Li et al, 2014). Understanding how the cell achieves optimal energy utilization critically depends on understanding how mRNA sequence features reliably drive ORF-specific translation
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