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Defining the anti-Shine-Dalgarno sequence interaction and quantifying its functional role in regulating translation efficiency
Open accessPreprint — published as 10.1098/rsob.160239 · Paper page
Abstract
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.
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Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 2×
“Transcription of the gene of interest is a necessary first step in the pathway of gene expression but, by itself, transcription is insufficient to ensure protein expression; studies in a variety of organisms have shown that mRNA abundances only modestly predict protein abundances (Guimaraes et al., 2014; Lu et al., 20…”
BackgroundLi, J. J., Bickel, P. J., & Biggin, M. D. (2014) · PeerJ · doi:10.7717/peerj.270 · Cited by 279
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Metadata
- Authors
- Hockenberry, A. J., Pah, A. R., Jewett, M. C., & Amaral, L. A. N.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Jewett, Michael C.
- Venue
- Open Biology
- Publisher
- openRxiv
- Published
- 2016-02-06
- Volume
- 7
- Issue
- 1
- Pages
- 160239-160239
- ISSN
- 2046-2441 (ISSN-L)
- PMC
- PMC5303271
- OpenAlex
- W2574962082
- Cited by
- 29
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 4
- FWCI
- 1.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Open Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (0943393, 1108350)
- U.S. Department of Defense (W911NF1410259)
- David and Lucile Packard Foundation (2011–37152)
- John Templeton Foundation (39147, FP053369-A//39147)
- Northwestern University
- National Institutes of Health (MCB-0943393)
- National Cancer Institute (P30CA060553)
- National Institute of General Medical Sciences (T32GM008061)
- Division of Materials Research
- Army Research Office (W911NF-14-1-0259, W911NF-14-1, W911NF)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- anti-Shine-Dalgarno sequence, translation efficiency, translation initiation, 5' untranslated region, sequence complementarity, prokaryotic ribosomes, mRNA secondary structure, nonlinear relationship, bacterial gene expression
- MeSH terms
- Bacteria, Base Sequence, Ribosomes, RNA, Bacterial, RNA, Messenger, Protein Biosynthesis, Genome, Bacterial, Codon, Initiator, 5' Untranslated Regions
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