Evidence map›Paper›PMID 29787767›Full record

ArticleJournal of molecular biology2018

Influence of gag and RRE Sequences on HIV-1 RNA Packaging Signal Structure and Function.

Siarhei Kharytonchyk, Joshua D Brown, Krista Stilger, Saif Yasin, Aishwarya S Iyer, John Collins, Michael F Summers, Alice Telesnitsky

Abstract read
In one paragraph

Article in Journal of molecular 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
–field-weighted citation impact
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.

  1. Transcription start site heterogeneity controls MDA5 sensing of unspliced HIV-1 RNAs.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. 5'-Cap sequestration is an essential determinant of HIV-1 genome packaging.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  10. Review
  11. HIV-based lentiviral vectors: origin and sequence differences.Molecular therapy. Methods & clinical development · 2021
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. HIV Rev-isited.Open biology · 2020
    Review
  17. Review
  18. Article
  19. 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.

Siarhei KharytonchykDepartment of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5620, United States.
Joshua D BrownHoward Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
Krista StilgerDepartment of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5620, United States.
Saif YasinHoward Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
Aishwarya S IyerHoward Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
John CollinsDepartment of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5620, United States.
Michael F SummersHoward Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, United States.
Alice TelesnitskyDepartment of Microbiology and Immunology, University of Michigan Medical School, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5620, United States. Electronic address: ateles@umich.edu.

Funding

NMR STUDIES OF RETROVIRAL NUCLEOCAPSID PROTEINSR01GM042561 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · PI SUMMERS, MICHAEL FINLEY · 1994 to 2019
$9.4M
Medical Scientist Training Program Administrative Supplement to Enhance Program Evaluation CapacityT32GM136561 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI Mary-Claire Roghmann · 2020 to 2026
$5.4M
Medical Scientist Training ProgramT32GM092237 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE · PI ROGHMANN, MARY-CLAIRE · 2010 to 2019
$3.0M
Influence of the 5´ Transcription Start Site Heterogeneity on HIV RNA Structure and FateF31GM123803 · NIGMS · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · PI BROWN, JOSHUA DAVID · 2017 to 2018
$38k
NIGMS NIH HHS F31 GM123803NIGMS NIH HHS R01 GM042561NIGMS NIH HHS T32 GM092237NIGMS NIH HHS T32 GM136561
6 · The paper itself

Abstract

The packaging signal (Ψ) and Rev-responsive element (RRE) enable unspliced HIV-1 RNAs' export from the nucleus and packaging into virions. For some retroviruses, engrafting Ψ onto a heterologous RNA is sufficient to direct encapsidation. In contrast, HIV-1 RNA packaging requires 5' leader Ψ elements plus poorly defined additional features. We previously defined minimal 5' leader sequences competitive with intact Ψ for HIV-1 packaging, and here examined the potential roles of additional downstream elements. The findings confirmed that together, HIV-1 5' leader Ψ sequences plus a nuclear export element are sufficient to specify packaging. However, RNAs trafficked using a heterologous export element did not compete well with RNAs using HIV-1's RRE. Furthermore, some RNA additions to well-packaged minimal vectors rendered them packaging-defective. These defects were rescued by extending gag sequences in their native context. To understand these packaging defects' causes, in vitro dimerization properties of RNAs containing minimal packaging elements were compared to RNAs with sequence extensions that were or were not compatible with packaging. In vitro dimerization was found to correlate with packaging phenotypes, suggesting that HIV-1 evolved to prevent 5' leader residues' base pairing with downstream residues and misfolding of the packaging signal. Our findings explain why gag sequences have been implicated in packaging and show that RRE's packaging contributions appear more specific than nuclear export alone. Paired with recent work showing that sequences upstream of Ψ can dictate RNA folds, the current work explains how genetic context of minimal packaging elements contributes to HIV-1 RNA fate determination.

Indexed as

Active Transport, Cell Nucleusgag Gene Products, Human Immunodeficiency VirusHEK293 CellsHIV-1HumansNucleic Acid Conformationrev Gene Products, Human Immunodeficiency VirusRNA, ViralVirus Assemblygag Gene Products, Human Immunodeficiency Virusrev Gene Products, Human Immunodeficiency VirusRNA, Viralfree energy calculationMfoldretrovirusRNA dimerizationRNA packaging

Identifiers

PMID29787767
PMCPMC6082134

What OpenQuestion holds

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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.