PT  - JOURNAL ARTICLE
AU  - Adam J. Hockenberry
AU  - Adam R. Pah
AU  - Michael C. Jewett
AU  - Luís A. Nunes Amaral
TI  - Defining the anti-Shine-Dalgarno sequence interaction and quantifying its functional role in regulating translation efficiency
AID  - 10.1101/038984
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 038984
4099  - http://biorxiv.org/content/early/2016/02/06/038984.short
4100  - http://biorxiv.org/content/early/2016/02/06/038984.full
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.