Evidence map›Paper›PMID 22929617›Full record

ArticleMolecular systems biology2012

Dynamics of protein noise can distinguish between alternate sources of gene-expression variability.

Abhyudai Singh, Brandon S Razooky, Roy D Dar, Leor S Weinberger

Abstract read
In one paragraph

Article in Molecular systems biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing 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

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

49 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Regulation of Transcriptional Bursting and Spatial Patterning in EarlybioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Journal of biosciences · 2022
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

4 authors.

Abhyudai SinghDepartment of Chemistry and Biochemistry, University of California, San Diego, CA, USA.
Brandon S Razooky
Roy D Dar
Leor S Weinberger

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
SYNTHETIC SYSTEMSP50GM085764 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, IDEKER, TREY · 2010 to 2018
$23.3M
Rewiring Therapeutic Cells: User-Controlled T Cells and Stem CellsP50GM081879 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A · 2010 to 2017
$19.0M
MOLECULAR BIOPHYSICS TRAINING PROGRAMT32GM008326 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOMIVES, ELIZABETH A. · 1989 to 2020
$7.5M
Developing Transmissible Antivirals by Exploiting Gene-Expression CircuitryDP2OD006677 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WEINBERGER, LEOR S · 2009 to 2009
$2.3M
NIAID NIH HHS P30 AI027763NIGMS NIH HHS GM08326NIGMS NIH HHS P50 GM081879NIGMS NIH HHS P50 GM085764NIGMS NIH HHS T32 GM008326NIH HHS DP2 OD006677NIH HHS DP2OD006677
6 · The paper itself

Abstract

Within individual cells, two molecular processes have been implicated as sources of noise in gene expression: (i) Poisson fluctuations in mRNA abundance arising from random birth and death of individual mRNA transcripts or (ii) promoter fluctuations arising from stochastic promoter transitions between different transcriptional states. Steady-state measurements of variance in protein levels are insufficient to discriminate between these two mechanisms, and mRNA single-molecule fluorescence in situ hybridization (smFISH) is challenging when cellular mRNA concentrations are high. Here, we present a perturbation method that discriminates mRNA birth/death fluctuations from promoter fluctuations by measuring transient changes in protein variance and that can operate in the regime of high molecular numbers. Conceptually, the method exploits the fact that transcriptional blockage results in more rapid increases in protein variability when mRNA birth/death fluctuations dominate over promoter fluctuations. We experimentally demonstrate the utility of this perturbation approach in the HIV-1 model system. Our results support promoter fluctuations as the primary noise source in HIV-1 expression. This study illustrates a relatively simple method that complements mRNA smFISH hybridization and can be used with existing GFP-tagged libraries to include or exclude alternate sources of noise in gene expression.

Indexed as

AlgorithmsCycloheximideDactinomycinFlavonoidsFlow CytometryGene ExpressionGene Expression ProfilingGenetic VariationGreen Fluorescent ProteinsHIV-1HumansIn Situ Hybridization, FluorescenceModels, GeneticNucleic Acid Synthesis InhibitorsPiperidinesPromoter Regions, GeneticalvocidibCycloheximideDactinomycinFlavonoidsGreen Fluorescent ProteinsNucleic Acid Synthesis InhibitorsPiperidinesProteinsProtein Synthesis InhibitorsRNA, Messenger

Identifiers

PMID22929617
PMCPMC3435505

What OpenQuestion holds

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LicenceCC BY-NC-SA
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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.