Evidence map›Paper›PMID 26674223›Full record

ArticleScientific reports2015

GC-elements controlling HRAS transcription form i-motif structures unfolded by heterogeneous ribonucleoprotein particle A1.

Giulia Miglietta, Susanna Cogoi, Erik B Pedersen, Luigi E Xodo

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

30 citing papers in PubMed, 64 citations in OpenAlex.

  1. Unraveling G-Quadruplex and i-Motif Coexistence Within a Double-Stranded DNA.Angewandte Chemie (International ed. in English) · 2026
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  15. Crystal Structure of an i-Motif from the HRAS Oncogene Promoter.Angewandte Chemie (International ed. in English) · 2023
    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 2 countries.

Giulia MigliettaDepartment of Medical and Biological Sciences, P.le Kolbe 4, 33100 Udine, Italy.
Susanna CogoiDepartment of Medical and Biological Sciences, P.le Kolbe 4, 33100 Udine, Italy.
Erik B PedersenNucleic Acid Center, Institute of Physics and Chemistry, University of Southern Denmark, DK-5230 Odense M, Denmark.
Luigi E XodoDepartment of Medical and Biological Sciences, P.le Kolbe 4, 33100 Udine, Italy.
University of Udine · ITUniversity of Southern Denmark · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

HRAS is regulated by two neighbouring quadruplex-forming GC-elements (hras-1 and hras-2), located upstream of the major transcription start sites (doi: 10.1093/nar/gku 5784). In this study we demonstrate that the C-rich strands of hras-1 and hras-2 fold into i-motif conformations (iMs) characterized under crowding conditions (PEG-300, 40% w/v) by semi-transitions at pH 6.3 and 6.7, respectively. Nondenaturing PAGE shows that the HRAS C-rich sequences migrate at both pH 5 and 7 as folded intramolecular structures. Chromatin immunoprecipitation shows that hnRNP A1 is associated under in vivo conditions to the GC-elements, while EMSA proves that hnRNP A1 binds tightly to the iMs. FRET and CD show that hnRNP A1 unfolds the iM structures upon binding. Furthermore, when hnRNP A1 is knocked out in T24 bladder cancer cells by a specific shRNA, the HRAS transcript level drops to 44 ± 5% of the control, suggesting that hnRNP A1 is necessary for gene activation. The sequestration by decoy oligonucleotides of the proteins (hnRNP A1 and others) binding to the HRAS iMs causes a significant inhibition of HRAS transcription. All these outcomes suggest that HRAS is regulated by a G-quadruplex/i-motif switch interacting with proteins that recognize non B-DNA conformations.

Indexed as

Protein UnfoldingBase SequenceCell Line, TumorCircular DichroismElectrophoresis, Polyacrylamide GelFluorescence Resonance Energy TransferGC Rich SequenceHeterogeneous Nuclear Ribonucleoprotein A1Heterogeneous-Nuclear Ribonucleoprotein Group A-BHumansHydrogen-Ion ConcentrationMolecular Sequence DataMutationNucleotide MotifsProtein BindingProto-Oncogene Proteins p21(ras)Heterogeneous Nuclear Ribonucleoprotein A1Heterogeneous-Nuclear Ribonucleoprotein Group A-BHRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID26674223
PMCPMC4682182
OpenAlexW2411316500

What OpenQuestion holds

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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.