Evidence map›Paper›PMID 25080493›Full record

ArticleMolecular systems biology2014

A 'resource allocator' for transcription based on a highly fragmented T7 RNA polymerase.

Thomas H Segall-Shapiro, Adam J Meyer, Andrew D Ellington, Eduardo D Sontag, Christopher A Voigt

Abstract read
In one paragraph

Article in Molecular systems biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
–field-weighted citation impact
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

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3 · Its place in the literature

Who cites it

84 citing papers in PubMed.

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24 more citing papers are in PubMed but not listed here.

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

5 authors.

Thomas H Segall-ShapiroDepartment of Biological Engineering, Synthetic Biology Center Massachusetts Institute of Technology, Cambridge, MA, USA.
Adam J MeyerInstitute for Cellular and Molecular Biology University of Texas at Austin, Austin, TX, USA.
Andrew D EllingtonInstitute for Cellular and Molecular Biology University of Texas at Austin, Austin, TX, USA.
Eduardo D SontagDepartment of Mathematics, Rutgers University, Piscataway, NJ, USA.
Christopher A VoigtDepartment of Biological Engineering, Synthetic Biology Center Massachusetts Institute of Technology, Cambridge, MA, USA cavoigt@gmail.com.

Funding

Characterization of Gradient-Responsive Genetic Programs Using Light SensorsR01GM095765 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VOIGT, CHRISTOPHER A · 2011 to 2014
$1.2M
NIGMS NIH HHS 5R01GM095765NIGMS NIH HHS R01 GM095765
6 · The paper itself

Abstract

Synthetic genetic systems share resources with the host, including machinery for transcription and translation. Phage RNA polymerases (RNAPs) decouple transcription from the host and generate high expression. However, they can exhibit toxicity and lack accessory proteins (σ factors and activators) that enable switching between different promoters and modulation of activity. Here, we show that T7 RNAP (883 amino acids) can be divided into four fragments that have to be co-expressed to function. The DNA-binding loop is encoded in a C-terminal 285-aa 'σ fragment', and fragments with different specificity can direct the remaining 601-aa 'core fragment' to different promoters. Using these parts, we have built a resource allocator that sets the core fragment concentration, which is then shared by multiple σ fragments. Adjusting the concentration of the core fragment sets the maximum transcriptional capacity available to a synthetic system. Further, positive and negative regulation is implemented using a 67-aa N-terminal 'α fragment' and a null (inactivated) σ fragment, respectively. The α fragment can be fused to recombinant proteins to make promoters responsive to their levels. These parts provide a toolbox to allocate transcriptional resources via different schemes, which we demonstrate by building a system which adjusts promoter activity to compensate for the difference in copy number of two plasmids.

Indexed as

Transcription, GeneticCloning, MolecularDNA Copy Number VariationsDNA-Directed RNA PolymerasesEscherichia coliGenetic EngineeringModels, GeneticMutationPlasmidsPromoter Regions, GeneticViral Proteinsbacteriophage T7 RNA polymeraseDNA-Directed RNA PolymerasesViral Proteinsgenetic circuitresource allocationsplit proteinsynthetic biologyT7 RNA polymerase

Identifiers

PMID25080493
PMCPMC4299498

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.