Evidence map›Paper›PMID 29883608›Full record

ArticleMolecular cell2018

Accessibility of the Shine-Dalgarno Sequence Dictates N-Terminal Codon Bias in E. coli.

Sanchari Bhattacharyya, William M Jacobs, Bharat V Adkar, Jin Yan, Wenli Zhang, Eugene I Shakhnovich

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Approaches for Studying Context Specificity of Translation Inhibitor Action.International journal of molecular sciences · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Sanchari BhattacharyyaDepartment of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, USA.
William M JacobsDepartment of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, USA.
Bharat V AdkarDepartment of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, USA.
Jin YanDepartment of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, USA; College of Chemical Engineering, Sichuan University, Chengdu 610065, Sichuan, China.
Wenli ZhangDepartment of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, USA; State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
Eugene I ShakhnovichDepartment of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA, USA. Electronic address: shakhnovich@chemistry.harvard.edu.
Harvard University · USSichuan University · CN

Funding

Study of Biological Evolution of Structure and Function in ProteinsR01GM068670 · NIGMS · HARVARD UNIVERSITY · PI SHAKHNOVICH, EUGENE I · 2004 to 2020
$7.0M
Biophysical mechanisms of proteomic and fitness effects of synonymous substitutionsR01GM124044 · NIGMS · HARVARD UNIVERSITY · PI SHAKHNOVICH, EUGENE I · 2017 to 2020
$1.3M
Kinetics of macromolecular complex assembly and regulationF32GM116231 · NIGMS · HARVARD UNIVERSITY · PI JACOBS, WILLIAM MONROE · 2016 to 2017
$112k
NIGMS NIH HHS F32 GM116231NIGMS NIH HHS R01 GM068670NIGMS NIH HHS R01 GM124044
6 · The paper itself

Abstract

Despite considerable efforts, no physical mechanism has been shown to explain N-terminal codon bias in prokaryotic genomes. Using a systematic study of synonymous substitutions in two endogenous E. coli genes, we show that interactions between the coding region and the upstream Shine-Dalgarno (SD) sequence modulate the efficiency of translation initiation, affecting both intracellular mRNA and protein levels due to the inherent coupling of transcription and translation in E. coli. We further demonstrate that far-downstream mutations can also modulate mRNA levels by occluding the SD sequence through the formation of non-equilibrium secondary structures. By contrast, a non-endogenous RNA polymerase that decouples transcription and translation largely alleviates the effects of synonymous substitutions on mRNA levels. Finally, a complementary statistical analysis of the E. coli genome specifically implicates avoidance of intra-molecular base pairing with the SD sequence. Our results provide general physical insights into the coding-level features that optimize protein expression in prokaryotes.

Indexed as

Codon, InitiatorNucleotide MotifsDNA-Directed RNA PolymerasesEscherichia coliEscherichia coli ProteinsGene Expression Regulation, BacterialGenome, BacterialNucleic Acid ConformationProtein BiosynthesisRNA, BacterialRNA, MessengerRNA StabilityStructure-Activity RelationshipTranscription, GeneticCodon, InitiatorDNA-Directed RNA PolymerasesEscherichia coli ProteinsRNA, BacterialRNA, Messenger

Identifiers

PMID29883608
PMCPMC6311106
OpenAlexW2951916095

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.