Evidence map›Paper›PMID 33443179›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Mfd regulates RNA polymerase association with hard-to-transcribe regions in vivo, especially those with structured RNAs.

Mark N Ragheb, Christopher Merrikh, Kaitlyn Browning, Houra Merrikh

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

18 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
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  3. Genome-wide strand-specific UV mutagenesis inProceedings of the National Academy of Sciences of the United States of America · 2025
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  8. Review
  9. Oxidative stress drives mutagenesis through transcription-coupled repair in bacteria.Proceedings of the National Academy of Sciences of the United States of America · 2023
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  10. Review
  11. Article
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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

4 authors at 2 institutions in 1 country.

Mark N RaghebMolecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195.ORCID 0000-0002-2790-9463
Christopher MerrikhDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37205.
Kaitlyn BrowningDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37205.ORCID 0000-0002-3064-0506
Houra MerrikhDepartment of Biochemistry, Vanderbilt University, Nashville, TN 37205 houra.merrikh@vanderbilt.edu.ORCID 0000-0001-9956-9640
Vanderbilt University · USUniversity of Washington · US

Funding

TRAINING PROGRAM IN ENVIRONMENTAL TOXICOLOGYT32ES007028 · NIEHS · VANDERBILT UNIVERSITY · PI F PETER Guengerich, Fiona Edith Harrison · 1985 to 2026
$15.7M
Mechanisms of antibiotic resistance development in bacterial pathogensR01AI127422 · NIAID · VANDERBILT UNIVERSITY · PI MERRIKH, HOURA · 2018 to 2021
$1.6M
Replication resolved in the living cell: Replisome dynamics, stability and structure.R01GM128191 · NIGMS · VANDERBILT UNIVERSITY · PI MERRIKH, HOURA, WIGGINS, PAUL A · 2018 to 2021
$1.4M
NIAID NIH HHS R01 AI127422NIEHS NIH HHS T32 ES007028NIGMS NIH HHS R01 GM128191
6 · The paper itself

Abstract

RNA polymerase (RNAP) encounters various roadblocks during transcription. These obstacles can impede RNAP movement and influence transcription, ultimately necessitating the activity of RNAP-associated factors. One such factor is the bacterial protein Mfd, a highly conserved DNA translocase and evolvability factor that interacts with RNAP. Although Mfd is thought to function primarily in the repair of DNA lesions that stall RNAP, increasing evidence suggests that it may also be important for transcription regulation. However, this is yet to be fully characterized. To shed light on Mfd's in vivo functions, we identified the chromosomal regions where it associates. We analyzed Mfd's impact on RNAP association and transcription regulation genome-wide. We found that Mfd represses RNAP association at many chromosomal regions. We found that these regions show increased RNAP pausing, suggesting that they are hard to transcribe. Interestingly, we noticed that the majority of the regions where Mfd regulates transcription contain highly structured regulatory RNAs. The RNAs identified regulate a myriad of biological processes, ranging from metabolism to transfer RNA regulation to toxin-antitoxin (TA) functions. We found that cells lacking Mfd are highly sensitive to toxin overexpression. Finally, we found that Mfd promotes mutagenesis in at least one toxin gene, suggesting that its function in regulating transcription may promote evolution of certain TA systems and other regions containing strong RNA secondary structures. We conclude that Mfd is an RNAP cofactor that is important, and at times critical, for transcription regulation at hard-to-transcribe regions, especially those that express structured regulatory RNAs.

Indexed as

Bacillus subtilisBacterial ProteinsDNADNA, BacterialDNA-Directed RNA PolymerasesDNA RepairEscherichia coliRNATranscription FactorsTranscription, GeneticBacterial ProteinsDNADNA, BacterialDNA-Directed RNA PolymerasesRNATranscription Factorstranscription repair coupling factor protein, BacteriaMfdmutagenesissmall RNAsTCR

Identifiers

PMID33443179
PMCPMC7817204
OpenAlexW3114363043

What OpenQuestion holds

Textmetadata
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.