Leveraging genome-wide datasets to quantify the functional role of the anti-Shine–Dalgarno sequence in regulating translation efficiency
Hockenberry AJ, Pah AR, Jewett MC, Amaral LANOpen Biology 7, 160239 (2017)
Abstract
Studies dating back to the 1970s established that sequence
complementarity
between the anti-Shine–Dalgarno (aSD) sequence on prokaryotic
ribosomes
and the 5’ untranslated region of mRNAs helps to facilitate translation
initiation. The optimal location of aSD sequence binding relative to
the
start codon, the full extents of the aSD sequence and the functional
form of
the relationship between aSD sequence complementarity and translation
efficiency
have not been fully resolved. Here, we investigate these relationships
by leveraging the sequence diversity of endogenous genes and recently
available
genome-wide estimates of translation efficiency. We show that—after
accounting for predicted mRNA structure—aSD sequence complementarity
increases the translation of endogenous mRNAs by roughly 50%. Further,
we observe that this relationship is nonlinear, with translation
efficiency
maximized for mRNAs with intermediate levels of aSD sequence
complementarity.
The mechanistic insights that we observe are highly robust: we
find nearly identical results in multiple datasets spanning three
distantly
related bacteria. Further, we verify our main conclusions by
re-analysing a
controlled experimental dataset.