Evidence map›Paper›PMID 29301786›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2018

Endogenous LINE-1 (Long Interspersed Nuclear Element-1) Reverse Transcriptase Activity in Platelets Controls Translational Events Through RNA-DNA Hybrids.

Hansjörg Schwertz, Jesse W Rowley, Gerald G Schumann, Ulrike Thorack, Robert A Campbell, Bhanu Kanth Manne, Guy A Zimmerman, Andrew S Weyrich, Matthew T Rondina

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 20% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. A New Role of NAP1L1 in Megakaryocytes and Human Platelets.International journal of molecular sciences · 2022
    Article
  6. Article
  7. Review
  8. Review
  9. Paclitaxel-induced stress granules increaseJournal of biomedical research · 2021
    Article
  10. Review
  11. Cytoplasmic synthesis of endogenousProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  12. Article
  13. Post-Transcriptional Expression Control in Platelet Biogenesis and Function.International journal of molecular sciences · 2020
    Review
  14. Article
  15. Annual Report on Sex in Preclinical Studies:Arteriosclerosis, thrombosis, and vascular biology · 2020
    Review
  16. Article
  17. Article
  18. New LINE(s) of Evidence for Genetic Regulation of Platelets.Arteriosclerosis, thrombosis, and vascular biology · 2018
    Article
  19. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Hansjörg SchwertzFrom the Molecular Medicine Program (H.S., J.W.R., R.A.C., B.K.M., G.A.Z., A.S.W., M.T.R.), Department of Internal Medicine (H.S., J.W.R., G.A.Z., A.S.W., M.T.R.), and Department of Surgery, Division of Vascular Surgery (H.S.), University of Utah, Salt Lake City; Department of Internal Medicine, George E. Wahlen Salt Lake City VAMC, UT (M.T.R.); Department of Immunology and Transfusion Medicine (U.T.) and Lichtenberg-Professor for Experimental Hemostasis (H.S.), University of Greifswald, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany (G.G.S.). hansjorg.schwertz@u2m2.utah.edu.
Jesse W RowleyFrom the Molecular Medicine Program (H.S., J.W.R., R.A.C., B.K.M., G.A.Z., A.S.W., M.T.R.), Department of Internal Medicine (H.S., J.W.R., G.A.Z., A.S.W., M.T.R.), and Department of Surgery, Division of Vascular Surgery (H.S.), University of Utah, Salt Lake City; Department of Internal Medicine, George E. Wahlen Salt Lake City VAMC, UT (M.T.R.); Department of Immunology and Transfusion Medicine (U.T.) and Lichtenberg-Professor for Experimental Hemostasis (H.S.), University of Greifswald, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany (G.G.S.).
Gerald G SchumannFrom the Molecular Medicine Program (H.S., J.W.R., R.A.C., B.K.M., G.A.Z., A.S.W., M.T.R.), Department of Internal Medicine (H.S., J.W.R., G.A.Z., A.S.W., M.T.R.), and Department of Surgery, Division of Vascular Surgery (H.S.), University of Utah, Salt Lake City; Department of Internal Medicine, George E. Wahlen Salt Lake City VAMC, UT (M.T.R.); Department of Immunology and Transfusion Medicine (U.T.) and Lichtenberg-Professor for Experimental Hemostasis (H.S.), University of Greifswald, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany (G.G.S.).
Ulrike ThorackFrom the Molecular Medicine Program (H.S., J.W.R., R.A.C., B.K.M., G.A.Z., A.S.W., M.T.R.), Department of Internal Medicine (H.S., J.W.R., G.A.Z., A.S.W., M.T.R.), and Department of Surgery, Division of Vascular Surgery (H.S.), University of Utah, Salt Lake City; Department of Internal Medicine, George E. Wahlen Salt Lake City VAMC, UT (M.T.R.); Department of Immunology and Transfusion Medicine (U.T.) and Lichtenberg-Professor for Experimental Hemostasis (H.S.), University of Greifswald, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany (G.G.S.).
Robert A CampbellFrom the Molecular Medicine Program (H.S., J.W.R., R.A.C., B.K.M., G.A.Z., A.S.W., M.T.R.), Department of Internal Medicine (H.S., J.W.R., G.A.Z., A.S.W., M.T.R.), and Department of Surgery, Division of Vascular Surgery (H.S.), University of Utah, Salt Lake City; Department of Internal Medicine, George E. Wahlen Salt Lake City VAMC, UT (M.T.R.); Department of Immunology and Transfusion Medicine (U.T.) and Lichtenberg-Professor for Experimental Hemostasis (H.S.), University of Greifswald, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany (G.G.S.).
Bhanu Kanth ManneFrom the Molecular Medicine Program (H.S., J.W.R., R.A.C., B.K.M., G.A.Z., A.S.W., M.T.R.), Department of Internal Medicine (H.S., J.W.R., G.A.Z., A.S.W., M.T.R.), and Department of Surgery, Division of Vascular Surgery (H.S.), University of Utah, Salt Lake City; Department of Internal Medicine, George E. Wahlen Salt Lake City VAMC, UT (M.T.R.); Department of Immunology and Transfusion Medicine (U.T.) and Lichtenberg-Professor for Experimental Hemostasis (H.S.), University of Greifswald, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany (G.G.S.).
Guy A ZimmermanFrom the Molecular Medicine Program (H.S., J.W.R., R.A.C., B.K.M., G.A.Z., A.S.W., M.T.R.), Department of Internal Medicine (H.S., J.W.R., G.A.Z., A.S.W., M.T.R.), and Department of Surgery, Division of Vascular Surgery (H.S.), University of Utah, Salt Lake City; Department of Internal Medicine, George E. Wahlen Salt Lake City VAMC, UT (M.T.R.); Department of Immunology and Transfusion Medicine (U.T.) and Lichtenberg-Professor for Experimental Hemostasis (H.S.), University of Greifswald, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany (G.G.S.).
Andrew S WeyrichFrom the Molecular Medicine Program (H.S., J.W.R., R.A.C., B.K.M., G.A.Z., A.S.W., M.T.R.), Department of Internal Medicine (H.S., J.W.R., G.A.Z., A.S.W., M.T.R.), and Department of Surgery, Division of Vascular Surgery (H.S.), University of Utah, Salt Lake City; Department of Internal Medicine, George E. Wahlen Salt Lake City VAMC, UT (M.T.R.); Department of Immunology and Transfusion Medicine (U.T.) and Lichtenberg-Professor for Experimental Hemostasis (H.S.), University of Greifswald, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany (G.G.S.).
Matthew T RondinaFrom the Molecular Medicine Program (H.S., J.W.R., R.A.C., B.K.M., G.A.Z., A.S.W., M.T.R.), Department of Internal Medicine (H.S., J.W.R., G.A.Z., A.S.W., M.T.R.), and Department of Surgery, Division of Vascular Surgery (H.S.), University of Utah, Salt Lake City; Department of Internal Medicine, George E. Wahlen Salt Lake City VAMC, UT (M.T.R.); Department of Immunology and Transfusion Medicine (U.T.) and Lichtenberg-Professor for Experimental Hemostasis (H.S.), University of Greifswald, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany (G.G.S.).
Universität Greifswald · DEGeorge E. Wahlen Department of VA Medical Center · US

Funding

UNIVERSITY OF UTAH CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE-UL1: BPCAUL1RR025764 · NCRR · UNIVERSITY OF UTAH · PI MCCLAIN, DONALD A. · 2008 to 2011
$19.4M
Translational Research Skills Development CoreU54HL112311 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S, ZIMMERMAN, GUY A. · 2012 to 2016
$12.9M
University of Utah Center for Clinical and Translational Science-UL1UL1TR000105 · NCATS · UNIVERSITY OF UTAH · PI MCCLAIN, DONALD A. · 2012 to 2013
$5.1M
TRANSLATIONAL EVENTS IN PLATELETSR01HL066277 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S · 2001 to 2012
$3.8M
Molecular Interactions of Myeloid Cells with EndotheliumR37HL044525 · NHLBI · UNIVERSITY OF UTAH · PI ZIMMERMAN, GUY A. · 2004 to 2013
$3.5M
The Effects of ART on Platelets and HIV-Associated ThrombosisR01HL126547 · NHLBI · UNIVERSITY OF UTAH · PI PLANELLES, VICENTE, RONDINA, MATTHEW THOMAS · 2014 to 2017
$3.0M
Platelet Immune Responses in Aging and InfluenzaR01AG048022 · NIA · UNIVERSITY OF UTAH · PI RONDINA, MATTHEW THOMAS · 2014 to 2018
$1.8M
The Platelet Metabolome in ObesityK01GM103806 · NIGMS · UNIVERSITY OF UTAH · PI ROWLEY, JESSE · 2012 to 2016
$802k
Novel Platelet Functions in Sepsis and Venous ThromboembolismK23HL092161 · NHLBI · UNIVERSITY OF UTAH · PI RONDINA, MATTHEW THOMAS · 2009 to 2013
$775k
The Regulation of Inflammatory Gene Responses in AgingR03AG040631 · NIA · UNIVERSITY OF UTAH · PI RONDINA, MATTHEW THOMAS · 2011 to 2012
$149k
NCRR NIH HHS UL1 RR025764NHLBI NIH HHS K23 HL092161NHLBI NIH HHS R01 HL066277NHLBI NIH HHS R01 HL126547NHLBI NIH HHS R37 HL044525NHLBI NIH HHS U54 HL112311NIA NIH HHS R01 AG048022NIA NIH HHS R03 AG040631NIGMS NIH HHS K01 GM103806
6 · The paper itself

Abstract

objectiveOne source of endogenous reverse transcriptase (eRT) activity in nucleated cells is the LINE-1/L1 (long interspersed nuclear element-1), a non-LTR retrotransposon that is implicated in the regulation of gene expression. Nevertheless, the presence and function of eRT activity and LINE-1 in human platelets, an anucleate cell, has not previously been determined. APPROACH AND

resultsWe demonstrate that human and murine platelets possess robust eRT activity and identify the source as being LINE-1 ribonucleoprotein particles. Inhibition of eRT in vitro in isolated platelets from healthy individuals or in people with HIV treated with RT inhibitors enhanced global protein synthesis and platelet activation. If HIV patients were treated with reverse transcriptase inhibitor, we found that platelets from these patients had increased basal activation. We next discovered that eRT activity in platelets controlled the generation of RNA-DNA hybrids, which serve as translational repressors. Inhibition of platelet eRT lifted this RNA-DNA hybrid-induced translational block and was sufficient to increase protein expression of target RNAs identified by RNA-DNA hybrid immunoprecipitation.

conclusionsThus, we provide the first evidence that platelets possess L1-encoded eRT activity. We also demonstrate that platelet eRT activity regulates platelet hyperreactivity and thrombosis and controls RNA-DNA hybrid formation and identify that RNA-DNA hybrids function as a novel translational control mechanism in human platelets.

Indexed as

Long Interspersed Nucleotide ElementsPlatelet ActivationProtein BiosynthesisAnimalsBlood PlateletsCell LineDisease Models, AnimalDNAFemaleHIV InfectionsHumansMaleMice, Inbred C57BLPulmonary EmbolismReverse Transcriptase InhibitorsRNADNAReverse Transcriptase InhibitorsRNARNA-Directed DNA Polymeraseblood plateletsmiceplatelet activationretroelementsthrombosis

Identifiers

PMID29301786
PMCPMC5864535
OpenAlexW2781546028

What OpenQuestion holds

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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.