Evidence map›Paper›PMID 23884411›Full record

ArticleThe Journal of biological chemistry2013

Negative elongation factor (NELF) coordinates RNA polymerase II pausing, premature termination, and chromatin remodeling to regulate HIV transcription.

Malini Natarajan, Gillian M Schiralli Lester, Chanhyo Lee, Anamika Missra, Gregory A Wasserman, Martin Steffen, David S Gilmour, Andrew J Henderson

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% 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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Premature transcription termination complex proteins PCF11 and WDR82 silence HIV-1 expression in latently infected cells.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Review
  13. Article
  14. Article
  15. Viruses in the Nucleus.Cold Spring Harbor perspectives in biology · 2021
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article
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

8 authors at 4 institutions in 2 countries.

Malini NatarajanFrom the Immunology and Infectious Diseases, Integrated Biosciences Graduate Program, Penn State University, University Park, Pennsylvania 16802,; the Departments of Medicine and Infectious Diseases.
Gillian M Schiralli Lesterthe Departments of Medicine and Infectious Diseases.
Chanhyo Leethe Departments of Medicine and Infectious Diseases.
Anamika Missrathe Department of Biochemistry and Molecular Biology, Penn State University, University Park, Pennsylvania 16802.
Gregory A WassermanMicrobiology, and.
Martin SteffenPathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118 and.
David S Gilmourthe Department of Biochemistry and Molecular Biology, Penn State University, University Park, Pennsylvania 16802.
Andrew J Hendersonthe Departments of Medicine and Infectious Diseases,; Microbiology, and. Electronic address: andrew.henderson@bmc.org.
Office of Infectious Diseases · USCzech Academy of Sciences, Institute of Microbiology · CZPennsylvania State University · USBoston University · US

Funding

Transcription mechanisms that contribute to HIV-1 latencyR01AI097117 · NIAID · BOSTON MEDICAL CENTER · PI HENDERSON, ANDREW J · 2013 to 2016
$1.7M
Regulation of HIV Transcription ElongationR01AI077463 · NIAID · BOSTON MEDICAL CENTER · PI HENDERSON, ANDREW J · 2009 to 2010
$834k
Transcriptional mechanisms that contribute to HIV-1 latencyR56AI097117 · NIAID · BOSTON MEDICAL CENTER · PI HENDERSON, ANDREW J · 2011 to 2011
$433k
NIAID NIH HHS AI077463NIAID NIH HHS AI097117NIAID NIH HHS R01 AI077463NIAID NIH HHS R01 AI097117NIAID NIH HHS R56 AI097117
6 · The paper itself

Abstract

A barrier to eradicating HIV infection is targeting and eliminating latently infected cells. Events that contribute to HIV transcriptional latency include repressive chromatin structure, transcriptional interference, the inability of Tat to recruit positive transcription factor b, and poor processivity of RNA polymerase II (RNAP II). In this study, we investigated mechanisms by which negative elongation factor (NELF) establishes and maintains HIV latency. Negative elongation factor (NELF) induces RNAP II promoter proximal pausing and limits provirus expression in HIV-infected primary CD4(+) T cells. Decreasing NELF expression overcomes RNAP II pausing to enhance HIV transcription elongation in infected primary T cells, demonstrating the importance of pausing in repressing HIV transcription. We also show that RNAP II pausing is coupled to premature transcription termination and chromatin remodeling. NELF interacts with Pcf11, a transcription termination factor, and diminishing Pcf11 in primary CD4(+) T cells induces HIV transcription elongation. In addition, we identify NCoR1-GPS2-HDAC3 as a NELF-interacting corepressor complex that is associated with repressed HIV long terminal repeats. We propose a model in which NELF recruits Pcf11 and NCoR1-GPS2-HDAC3 to paused RNAP II, reinforcing repression of HIV transcription and establishing a critical checkpoint for HIV transcription and latency.

Indexed as

Chromatin Assembly and DisassemblyModels, BiologicalTranscription Elongation, GeneticTranscription Termination, GeneticCD4-Positive T-LymphocytesHistone Deacetylase 3Histone DeacetylasesHIV-1HIV InfectionsHumansIntracellular Signaling Peptides and ProteinsJurkat CellsmRNA Cleavage and Polyadenylation FactorsNuclear Receptor Co-Repressor 1RNA Polymerase IITranscription FactorsGPS2 protein, humanHistone Deacetylase 3Histone DeacetylasesIntracellular Signaling Peptides and ProteinsmRNA Cleavage and Polyadenylation FactorsNCOR1 protein, humanNSMF protein, humanNuclear Receptor Co-Repressor 1Pcf11 protein, humanRNA Polymerase IITranscription FactorsHIVRNA Polymerase IITranscription Elongation FactorsTranscription RegulationTranscription Repressor

Identifiers

PMID23884411
PMCPMC3764804
OpenAlexW2081540048

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.