RT Journal Article SR Electronic T1 Defining the anti-Shine-Dalgarno sequence interaction and quantifying its functional role in regulating translation efficiency JF bioRxiv FD Cold Spring Harbor Laboratory SP 038984 DO 10.1101/038984 A1 Adam J. Hockenberry A1 Adam R. Pah A1 Michael C. Jewett A1 Luís A. Nunes Amaral YR 2016 UL http://biorxiv.org/content/early/2016/02/06/038984.abstract AB Summary Studies dating back to the 1970s established that binding between the anti-Shine-Dalgarno (aSD) sequence on prokaryotic ribosomes and mRNA helps to facilitate translation initiation. The location of aSD binding relative to the start codon, the full extents of the aSD sequence, and the functional form of the relationship between aSD binding and translation efficiency are important parameters that remain ill defined in the literature. Here, we leverage genome-wide estimates of translation efficiency to determine these parameters and show that anti-Shine-Dalgarno sequence binding increases the translation of endogenous mRNAs on the order of 50%. Our findings highlight the non-linearity of this relationship, showing that translation efficiency is maximized for sequences with intermediate aSD binding strengths. These mechanistic insights are highly robust; we find nearly identical results in ribosome profiling datasets from 3 highly diverged bacteria, as well as independent genome-scale estimates and controlled experimental data using recombinant GFP expression.