Evidence map›Paper›PMID 30973829›Full record

ArticleJCI insight2019

Detection of circulating extracellular mRNAs by modified small-RNA-sequencing analysis.

Kemal M Akat, Youngmin A Lee, Arlene Hurley, Pavel Morozov, Klaas Ea Max, Miguel Brown, Kimberly Bogardus, Anuoluwapo Sopeyin, Kai Hildner, Thomas G Diacovo and 3 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

39 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Extracellular RNAs as Messengers and Early Biomarkers in Neurodegeneration.International journal of molecular sciences · 2025
    Review
  5. Review
  6. Article
  7. Article
  8. Article
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  11. Article
  12. The tRNAProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  13. Article
  14. Article
  15. Review
  16. Review
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  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

13 authors at 5 institutions in 3 countries.

Kemal M AkatLaboratory of RNA Molecular Biology and.
Youngmin A LeeLaboratory of RNA Molecular Biology and.
Arlene HurleyCenter for Translational Science, The Rockefeller University, New York, New York, USA.
Pavel MorozovLaboratory of RNA Molecular Biology and.
Klaas Ea MaxLaboratory of RNA Molecular Biology and.
Miguel BrownLaboratory of RNA Molecular Biology and.
Kimberly BogardusLaboratory of RNA Molecular Biology and.
Anuoluwapo SopeyinLaboratory of RNA Molecular Biology and.
Kai HildnerDepartment of Medicine 1, University Hospital Erlangen, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Bavaria, Germany.
Thomas G DiacovoDepartments of Pediatrics and Cell Biology and Pathology, Columbia University Medical Center, New York, New York, USA.
Markus F NeurathDepartment of Medicine 1, University Hospital Erlangen, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research, Erlangen, Bavaria, Germany.
Martin BorggrefeFirst Department of Medicine, University Medical Center Mannheim, Faculty of Medicine Mannheim, University of Heidelberg, European Center for AngioScience, and DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, Mannheim, Baden-Wuerttemberg, Germany.
Thomas TuschlLaboratory of RNA Molecular Biology and.
MRC Laboratory of Molecular Biology · GBUniversitätsklinikum Erlangen · DEColumbia University Irving Medical Center · USHeidelberg University · DERockefeller University · US

Funding

Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8M
Placenta-derived extracellular circulating RNA as a tool for monitoring placental functionR01HD086327 · NICHD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI WILLIAMS, ZEV · 2015 to 2019
$3.8M
Clinical utility of extracellular RNA as marker of kidney disease progressionUH3TR000933 · NCATS · ROCKEFELLER UNIVERSITY · PI SUTHANTHIRAN, MANIKKAM, TUSCHL, THOMAS · 2015 to 2017
$2.5M
NCATS NIH HHS UH3 TR000933NCATS NIH HHS UL1 TR000043NICHD NIH HHS R01 HD086327
6 · The paper itself

Abstract

Extracellular mRNAs (ex-mRNAs) potentially supersede extracellular miRNAs (ex-miRNAs) and other RNA classes as biomarkers. We performed conventional small-RNA-sequencing (sRNA-seq) and sRNA-seq with T4 polynucleotide kinase (PNK) end-treatment of total exRNA isolated from serum and platelet-poor EDTA, ACD, and heparin plasma to study the effect on ex-mRNA capture. Compared to conventional sRNA-seq PNK-treatment increased the detection of informative ex-mRNAs reads up to 50-fold. The exRNA pool was dominated by hematopoietic cells and platelets, with additional contribution from the liver. About 60% of the 15- to 42-nt reads originated from the coding sequences, in a pattern reminiscent of ribosome-profiling. Blood sample type had a considerable influence on the exRNA profile. On average approximately 350 to 1,100 distinct ex-mRNA transcripts were detected depending on plasma type. In serum, additional transcripts from neutrophils and hematopoietic cells increased this number to near 2,300. EDTA and ACD plasma showed a destabilizing effect on ex mRNA and non-coding RNA ribonucleoprotein complexes compared to other plasma types. In a proof-of-concept study, we investigated differences between the exRNA profiles of patients with acute coronary syndrome (ACS) and healthy controls. The improved tissue resolution of ex mRNAs after PNK-treatment enabled us to detect a neutrophil-signature in ACS that escaped detection by ex miRNA analysis.

Indexed as

Acute Coronary SyndromeAdultAgedBiomarkersBlood CellsCase-Control StudiesCell-Free Nucleic AcidsCitric AcidEdetic AcidErythrocytesFemaleGlucoseHeparinHigh-Throughput Nucleotide SequencingHumansLeukocytes, Mononuclearacid citrate dextroseBiomarkersCell-Free Nucleic AcidsCitric AcidEdetic AcidGlucoseHeparinPolynucleotide 5'-Hydroxyl-KinaseBioinformaticsCardiologyMolecular diagnosisRNA processingVascular Biology

Identifiers

PMID30973829
PMCPMC6538341
OpenAlexW2908004981

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.