Evidence map›Paper›PMID 30001206›Full record

ArticleGenome biology2018

Alternative DNA secondary structure formation affects RNA polymerase II promoter-proximal pausing in human.

Karol Szlachta, Ryan G Thys, Naomi D Atkin, Levi C T Pierce, Stefan Bekiranov, Yuh-Hwa Wang

Abstract read
In one paragraph

Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing 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

42 citing papers in PubMed.

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  10. Microbiology and molecular biology reviews : MMBR · 2024
    Review
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  16. DNA language models are powerful predictors of genome-wide variant effects.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  17. Review
  18. Review
  19. 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

6 authors.

Karol SzlachtaDepartment of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908-0733, USA.
Ryan G ThysDepartment of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908-0733, USA.
Naomi D AtkinDepartment of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908-0733, USA.
Levi C T PierceRelay Therapeutics, Inc., Cambridge, MA, 02142, USA.
Stefan BekiranovDepartment of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908-0733, USA. sb3de@virginia.edu.
Yuh-Hwa WangDepartment of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908-0733, USA. yw4b@virginia.edu.ORCID 0000-0002-9804-9368

Funding

Cancer Research Training Program: From Molecular Mechanisms to Therapeutic StrategiesT32CA009109 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Andrew Carl Dudley, Melanie R Rutkowski · 1985 to 2026
$13.9M
Genome-wide DNA Secondary Structure Analysis to Investigate DNA FragilityR01GM101192 · NIGMS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WANG, YUH-HWA · 2013 to 2024
$2.8M
The Role of Fragile Sites in RET/PTC RearrangementR01CA113863 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WANG, YUH-HWA · 2006 to 2018
$2.5M
NCI NIH HHS R01 CA113863NCI NIH HHS T32 CA009109NIGMS NIH HHS R01 GM101192NIGMS NIH HHS RO1GM101192
6 · The paper itself

Abstract

backgroundAlternative DNA secondary structures can arise from single-stranded DNA when duplex DNA is unwound during DNA processes such as transcription, resulting in the regulation or perturbation of these processes. We identify sites of high propensity to form stable DNA secondary structure across the human genome using Mfold and ViennaRNA programs with parameters for analyzing DNA.

resultsThe promoter-proximal regions of genes with paused transcription are significantly and energetically more favorable to form DNA secondary structure than non-paused genes or genes without RNA polymerase II (Pol II) binding. Using Pol II ChIP-seq, GRO-seq, NET-seq, and mNET-seq data, we arrive at a robust set of criteria for Pol II pausing, independent of annotation, and find that a highly stable secondary structure is likely to form about 10-50 nucleotides upstream of a Pol II pausing site. Structure probing data confirm the existence of DNA secondary structures enriched at the promoter-proximal regions of paused genes in human cells. Using an in vitro transcription assay, we demonstrate that Pol II pausing at HSPA1B, a human heat shock gene, is affected by manipulating DNA secondary structure upstream of the pausing site.

conclusionsOur results indicate alternative DNA secondary structure formation as a mechanism for how GC-rich sequences regulate RNA Pol II promoter-proximal pausing genome-wide.

Indexed as

DNAGenome, HumanHumansNucleotidesPromoter Regions, GeneticRNA Polymerase IITranscription, GeneticDNANucleotidesRNA Polymerase IIDNA secondary structureRNA polymerase II promoter-proximal pausing

Identifiers

PMID30001206
PMCPMC6042338

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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.