Evidence map›Paper›PMID 27048800›Full record

ArticlemBio2016

The CpxQ sRNA Negatively Regulates Skp To Prevent Mistargeting of β-Barrel Outer Membrane Proteins into the Cytoplasmic Membrane.

Marcin Grabowicz, Daria Koren, Thomas J Silhavy

Open access · goldAbstract read
In one paragraph

Article in mBio, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
8.7field-weighted citation impact, top 2% 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

47 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. ThemBio · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. The global RNA-RNA interactome ofProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. The sacrificial adaptor protein Skp functions to remove stalled substrates from the β-barrel assembly machine.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  17. Article
  18. Novel Insight into the Effects of CpxR onInternational journal of molecular sciences · 2021
    Article
  19. Homeostasis of the Gram-negative cell envelope.Current opinion in microbiology · 2021
    Review
  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

3 authors at 1 institution in 1 country.

Marcin GrabowiczDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, USA.ORCID http://orcid.org/0000-0001-8000-2222
Daria KorenDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Thomas J SilhavyDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, USA tsilhavy@princeton.edu.
Princeton University · US

Funding

Biogenesis and maintenance of the outer membrane of Gram-negative bacteriaR35GM118024 · NIGMS · PRINCETON UNIVERSITY · PI SILHAVY, THOMAS J. · 2016 to 2025
$8.1M
GENETIC ANALYSIS OF PROTEIN EXPORTR37GM034821 · NIGMS · PRINCETON UNIVERSITY · PI SILHAVY, THOMAS J. · 1999 to 2008
$4.9M
GENETIC ANALYSIS OF PROTEIN EXPORTR01GM034821 · NIGMS · PRINCETON UNIVERSITY · PI SILHAVY, THOMAS J. · 1985 to 2015
$4.7M
NIGMS NIH HHS GM34821NIGMS NIH HHS R01 GM034821NIGMS NIH HHS R35 GM118024NIGMS NIH HHS R37 GM034821
6 · The paper itself

Abstract

unlabelledThe promoter most strongly induced upon activation of the Cpx two-component envelope stress response is the cpxP promoter. The 3' untranscribed region (UTR) of the cpxP transcript is shown to produce a small RNA (sRNA), CpxQ. We investigated the role of CpxQ in combating envelope stress. Remarkably, the two effectors specified by the transcript are deployed to combat distinct stresses in different cellular compartments. CpxP acts in both a regulatory negative-feedback loop and as an effector that combats periplasmic protein misfolding. We find that CpxQ combats toxicity at the inner membrane (IM) by downregulating the synthesis of the periplasmic chaperone Skp. Our data indicate that this regulation prevents Skp from inserting β-barrel outer membrane proteins (OMPs) into the IM, a lethal event that likely collapses the proton motive force. Our findings suggest that Skp can fold and directly insert OMPs into a lipid bilayer in vivo without the aid of the Bam complex. IMPORTANCE: Skp is a well-characterized periplasmic chaperone that binds unfolded OMPs. Surprisingly, we find that Skp can catalyze the folding and mistargeting of OMPs into the inner membrane without the aid of the other cellular proteins that normally assemble OMPs. Several OMPs function as diffusion pores. Accordingly, their mistargeting is lethal because it depolarizes the inner membrane. We show that the most highly expressed transcript of the Cpx stress response produces an sRNA from the 3' UTR, CpxQ, which combats this potential toxicity by downregulating Skp production. Defects in OMP assembly trigger the σ(E)response to upregulate factors, including Skp, that promote OMP folding. The Cpx response downregulates σ(E) Our findings reveal that this heretofore puzzling hierarchy exists to protect the inner membrane.

Indexed as

Gene Expression Regulation, BacterialCell MembraneDNA-Binding ProteinsEscherichia coliEscherichia coli ProteinsMolecular ChaperonesPeriplasmProtein FoldingProtein TransportRNA, BacterialDNA-Binding ProteinsEscherichia coli ProteinsMolecular ChaperonesRNA, BacterialSkp protein, E coli

Identifiers

PMID27048800
PMCPMC4817254
OpenAlexW2317375723

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.