Evidence map›Paper›PMID 26844769›Full record

ArticlePLoS computational biology2016

MicroRNAs Form Triplexes with Double Stranded DNA at Sequence-Specific Binding Sites; a Eukaryotic Mechanism via which microRNAs Could Directly Alter Gene Expression.

Steven W Paugh, David R Coss, Ju Bao, Lucas T Laudermilk, Christy R Grace, Antonio M Ferreira, M Brett Waddell, Granger Ridout, Deanna Naeve, Michael Leuze and 8 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00137111 (Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia), which is not on this map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.2field-weighted citation impact, top 4% 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.

NCT00137111 phase3completednot on this map

Total XV - Total Therapy Study XV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia

TypeinterventionalSponsorSt. Jude Children's Research HospitalRan2000 to 2014Enrolled501ConditionsLymphoblastic Leukemia, AcuteArmsPrednisone, Dexamethasone, Vincristine, Daunorubicin, Doxorubicin, L-asparaginase, PEG-L-asparaginase, Erwinia asparaginase, Methotrexate, Cyclophosphamide, Cytarabine, Etoposide, Mercaptopurine, Imatinib, chemotherapy, intrathecal chemotherapy
3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 88 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. MicroRNAs as Endocrine Modulators of Breast Cancer.International journal of molecular sciences · 2025
    Review
  6. Review
  7. Article
  8. Easy triplex: An online tool for predicting the formation of DNA-RNA triple helices.Computational and structural biotechnology journal · 2025
    Article
  9. Nuclear miRNAs: Gene Regulation Activities.International journal of molecular sciences · 2024
    Review
  10. Participation of miR165a in the Phytochrome Signal Transduction in Maize (International journal of molecular sciences · 2024
    Article
  11. Special Issue "Bioinformatics of Unusual DNA and RNA Structures".International journal of molecular sciences · 2024
    Article
  12. Article
  13. Noncanonical functions of microRNAs in the nucleus.Acta biochimica et biophysica Sinica · 2024
    Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review
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

18 authors at 3 institutions in 2 countries.

Steven W PaughHematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
David R CossHigh Performance Computing Facility, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Ju BaoDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Lucas T LaudermilkHematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Christy R GraceDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Antonio M FerreiraHigh Performance Computing Facility, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
M Brett WaddellMolecular Interaction Analysis Laboratory, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Granger RidoutFunctional Genomics Laboratory, Hartwell Center for Bioinformatics & Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Deanna NaeveFunctional Genomics Laboratory, Hartwell Center for Bioinformatics & Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Michael LeuzeComputer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.
Philip F LoCascioDoctoral Training Centre, University of Oxford, Oxford, United Kingdom.
John C PanettaDepartment of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Mark R WilkinsonHematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Ching-Hon PuiHematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Clayton W NaeveDepartment of Information Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Edward C UberbacherComputer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, United States of America.
Erik J BontenHematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
William E EvansHematological Malignancies Program, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
St. Jude Children's Research Hospital · USOak Ridge National Laboratory · USUniversity of Oxford · GB

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
CPML - Project 3: Genome-wide Studies of Adverse EffectsP50GM115279 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI RELLING, MARY V · 2015 to 2019
$15.1M
PHARMACOGENOMICS OF CHILDHOOD LEUKEMIA (ALL)R37CA036401 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI EVANS, WILLIAM E · 1987 to 2014
$9.7M
PAARK4Kids-Pharmacogenomics of Anticancer Agents Research in ChildrenU01GM092666 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI RELLING, MARY V · 2010 to 2014
$8.9M
MicroRNA pharmacogenomics: implications for childhood leukemia (ALL)F32CA141762 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI PAUGH, STEVEN WILLIAM · 2009 to 2011
$157k
NCI NIH HHS CA 21765NCI NIH HHS F32 CA141762NCI NIH HHS P30 CA021765NCI NIH HHS R37 CA036401NCI NIH HHS R37 CA36401NIGMS NIH HHS P50 GM115279NIGMS NIH HHS U01 GM092666NIGMS NIH HHS U01 GM92666
6 · The paper itself

Abstract

MicroRNAs are important regulators of gene expression, acting primarily by binding to sequence-specific locations on already transcribed messenger RNAs (mRNA) and typically down-regulating their stability or translation. Recent studies indicate that microRNAs may also play a role in up-regulating mRNA transcription levels, although a definitive mechanism has not been established. Double-helical DNA is capable of forming triple-helical structures through Hoogsteen and reverse Hoogsteen interactions in the major groove of the duplex, and we show physical evidence (i.e., NMR, FRET, SPR) that purine or pyrimidine-rich microRNAs of appropriate length and sequence form triple-helical structures with purine-rich sequences of duplex DNA, and identify microRNA sequences that favor triplex formation. We developed an algorithm (Trident) to search genome-wide for potential triplex-forming sites and show that several mammalian and non-mammalian genomes are enriched for strong microRNA triplex binding sites. We show that those genes containing sequences favoring microRNA triplex formation are markedly enriched (3.3 fold, p<2.2 × 10(-16)) for genes whose expression is positively correlated with expression of microRNAs targeting triplex binding sequences. This work has thus revealed a new mechanism by which microRNAs could interact with gene promoter regions to modify gene transcription.

Indexed as

AlgorithmsBase CompositionBase SequenceBinding SitesComputational BiologyDNAGene Expression RegulationHumansLeukemiaMicroRNAsDNAMicroRNAstriplex DNA

Identifiers

PMID26844769
PMCPMC4742280
OpenAlexW2261001639

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.