Depletion of Shine-Dalgarno Sequences Within Bacterial Coding Regions Is Expression Dependent

Abstract

Efficient and accurate protein synthesis is crucial for organismal survival in competitive environments. Translation efficiency (the number of proteins translated from a single mRNA in a given time period) is the combined result of differential translation initiation, elongation, and termination rates. Previous research identified the Shine-Dalgarno (SD) sequence as a modulator of translation initiation in bacterial genes, while codon usage biases are frequently implicated as a primary determinant of elongation rate variation. Recent studies have suggested that SD sequences within coding sequences may negatively affect translation elongation speed, but this claim remains controversial. Here, we present a metric to quantify the prevalence of SD sequences in coding regions. We analyze hundreds of bacterial genomes and find that the coding sequences of highly expressed genes systematically contain fewer SD sequences than expected, yielding a robust correlation between the normalized occurrence of SD sites and protein abundances across a range of bacterial taxa. We further show that depletion of SD sequences within ribosomal protein genes is correlated with organismal growth rates, supporting the hypothesis of strong selection against the presence of these sequences in coding regions and suggesting their association with translation efficiency in bacteria.

Prokaryotic rRNA-mRNA interactions are involved in all translation steps and shape bacterial transcripts

“…Importantly, this selection was also observed away from positions that are upstream of a nearby AUG, suggesting that such selection is also related to elongation, and not just to avoiding internal translation initiation ( Figure S2 and Supplementary section S.2). Our findings are in agreement with those of Yang et al (19) who showed depletion in internal-SD-like sequences in most species analyzed (without a control for the positions that are close to an AUG). However, this study provides this insight at a much higher resolution: Yang et al examined the occurrence of such sequences over the total genome whereas we performed a per-position comparison in each genome.…”

“…Previous work has identified pieces of this puzzle, such as the importance of the aSD-SD interactions for translation initiation(1, 2), and some initial evidences that these interactions may be deleterious in the coding regions (19,35). This study is novel in expanding our understanding of the effect of such interactions throughout the translation process -from pre-initiation small sub-unit diffusion, through initiation, elongation, and termination.…”

“…Ribo-seq analyses in E. coli have indicated that strong interactions between the 16S rRNA and the mRNA can lead to pauses during translation elongation, hindering translation (9)(10)(11)(12)19) ( Figure 2D). Avoiding such strong rRNA-mRNA interactions in the coding region should thus allow the ribosome to flow efficiently during translation elongation.…”

Comparative genomic analysis of translation initiation mechanisms for genes lacking the Shine–Dalgarno sequence in prokaryotes

“…Indeed, it was recently reported that highly expressed genes tend to contain fewer SD-like sequences in coding regions, which was observed in various species of prokaryotes (37,38). Interestingly, Starmer et al.…”

Adenine Enrichment at the Fourth CDS Residue in Bacterial Genes Is Consistent with Error Proofing for +1 Frameshifts

“…There are claims that the CDS is under selection to bind transcription factors ( Stergachis et al 2013 ), although these are contested ( Xing and He 2015 ; Agoglia and Fraser 2016 ). Selection might be for avoidance of, rather than selection for, certain motifs, such as intra-CDS Shine–Dalgarno (SD)-like sequences ( Diwan and Agashe 2016 ; Yang et al 2016 ), or motifs for RNA binding proteins that bind to introns are avoided within CDSs ( Savisaar and Hurst 2017 ).…”