Evidence map›Paper›PMID 21149457›Full record

ArticleThe Journal of biological chemistry2011

Mechanism of down-regulation of RNA polymerase III-transcribed non-coding RNA genes in macrophages by Leishmania.

Tanu Rana, Smita Misra, Mukul K Mittal, Anitra L Farrow, Keith T Wilson, MacRae F Linton, Sergio Fazio, Ian M Willis, Gautam Chaudhuri

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

16 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Frontiers in immunology · 2019
    Review
  7. Article
  8. Maf1, A New PTEN Target Linking RNA and Lipid Metabolism.Trends in endocrinology and metabolism: TEM · 2016
    Review
  9. Article
  10. Involvement of RNA Polymerase III in Immune Responses.Molecular and cellular biology · 2015
    Article
  11. Article
  12. Article
  13. Article
  14. Alu elements: know the SINEs.Genome biology · 2011
    Review
  15. Article
  16. 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

9 authors at 3 institutions in 1 country.

Tanu RanaDepartment of Microbiology and Immunology, Meharry Medical College, Nashville, Tennessee 37208, USA.
Smita Misra
Mukul K Mittal
Anitra L Farrow
Keith T Wilson
MacRae F Linton
Sergio Fazio
Ian M Willis
Gautam Chaudhuri
Meharry Medical College · USVanderbilt University · USAlbert Einstein College of Medicine · US

Funding

THE MEHARRY RISE INITIATIVER25GM059994 · NIGMS · MEHARRY MEDICAL COLLEGE · PI MOTLEY-JOHNSON, EVANGELINE D · 1999 to 2021
$23.0M
THE MOLECULAR BASIS OF BARTONELLA BACILLIFORMIS PATHOGENICITYS06GM008037 · NIGMS · MEHARRY MEDICAL COLLEGE · PI RUCKER, HUBERT K. · 1989 to 2007
$17.5M
FUNCTIONAL HIERARCHY OF REMNANT LIPOPROTEIN RECEPTORSR01HL057986 · NHLBI · VANDERBILT UNIVERSITY · PI FAZIO, SERGIO · 1998 to 2016
$6.2M
Immunomodulatory effects of arginine supplementation in colitis and colon cancerR01AT004821 · NCCIH · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 2008 to 2017
$4.0M
MOLECULAR PARASITOLOGY TRAINING PROGRAMT32AI007281 · NIAID · MEHARRY MEDICAL COLLEGE · PI NDE, PIUS N · 1985 to 2025
$3.2M
MACROPHAGE EXPRESSION OF APOAI AND ATHEROSCLEROSISR01HL065709 · NHLBI · VANDERBILT UNIVERSITY · PI FAZIO, SERGIO · 2000 to 2008
$3.2M
Transcriptional Repression by Maf1 in YeastR01GM085177 · NIGMS · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI WILLIS, IAN M · 2009 to 2012
$2.1M
SRP RNA level as a determinant of leishmanial parasitism of macrophagesR21AI076757 · NIAID · MEHARRY MEDICAL COLLEGE · PI CHAUDHURI, GAUTAM · 2008 to 2009
$391k
DNA ANTISENSE APPROACH AGAINST LEISHMANIASISR01AI042327 · NIAID · MEHARRY MEDICAL COLLEGE · PI CHAUDHURI, GAUTAM · 1998 to 2000
$217k
NCCIH NIH HHS R01 AT004821NHLBI NIH HHS R01 HL057986NHLBI NIH HHS R01 HL065709NHLBI NIH HHS R01HL57986NHLBI NIH HHS R01HL65709NIAID NIH HHS 1R21AI076757-01A1NIAID NIH HHS 2T32AI007281-21A1NIAID NIH HHS 5R01AI042327NIAID NIH HHS R21 AI076757NIAID NIH HHS T32 AI007281NIGMS NIH HHS 1R01GM085177NIGMS NIH HHS 3 S06 GM008037-34-S2NIGMS NIH HHS 5R25GM059994-10NIGMS NIH HHS R01 GM085177NIGMS NIH HHS R25 GM059994NIGMS NIH HHS S06 GM008037
6 · The paper itself

Abstract

The parasitic protozoan Leishmania invades mammalian macrophages to establish infection. We reported previously that Leishmania manipulates the expression of several non-coding RNA genes (e.g. Alu RNA, B1 RNA, and signal recognition particle RNA) in macrophages to favor the establishment of their infection in the phagolysosomes of these cells (Ueda, Y., and Chaudhuri, G. (2000) J. Biol. Chem. 275, 19428-19432; Misra, S., Tripathi, M. K., and Chaudhuri, G. (2005) J. Biol. Chem. 280, 29364-29373). We report here the mechanism of this down-regulation. We found that the non-coding RNA (ncRNA) genes that are repressed by Leishmania infection in macrophages contain a "B-box" in their promoters and thus require the polymerase III transcription factor TFIIIC for their expression. We also found that Leishmania promastigotes through their surface protease (leishmanolysin or gp63) activate the thrombin receptor PAR1 in the macrophages. This activation of PAR1 raised the cytosolic concentration of Ca(2+) into the micromolar range, thereby activating the Ca(2+)-dependent protease μ-calpain. μ-Calpain then degraded TFIIIC110 to inhibit the expression of the selected ncRNA genes. Avirulent stocks of Leishmania not expressing surface gp63 failed to down-regulate ncRNAs in the exposed macrophages. Inhibition of PAR1 or calpain 1 in macrophages made them resistant to Leishmania infection. These data suggest that macrophage PAR1 and calpain 1 are potential drug targets against leishmaniasis.

Indexed as

Down-RegulationAnimalsCalciumCalpainCell Line, TumorHumansLeishmania majorLeishmaniasis, CutaneousMacrophagesMetalloendopeptidasesMiceReceptor, PAR-1RNA Polymerase IIIRNA, UntranslatedTranscription Factors, TFIIITranscription Factor TFIIICCalciumCalpainCapn1 protein, mouseglycoprotein gp63, LeishmaniaMetalloendopeptidasesReceptor, PAR-1RNA Polymerase IIIRNA, UntranslatedTranscription Factors, TFIIITranscription Factor TFIIIC

Identifiers

PMID21149457
PMCPMC3057815
OpenAlexW2014535116

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.