Evidence map›Paper›PMID 21515677›Full record

ArticleThe Journal of biological chemistry2011

Identification of cis-acting elements in the 3'-untranslated region of the dengue virus type 2 RNA that modulate translation and replication.

Mark Manzano, Erin D Reichert, Stephanie Polo, Barry Falgout, Wojciech Kasprzak, Bruce A Shapiro, Radhakrishnan Padmanabhan

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 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
7.8field-weighted citation impact, top 3% 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

72 citing papers in PubMed, 107 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Zika Virus: A Tale of Two Lineages.Pathogens (Basel, Switzerland) · 2025
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. West Nile virus unmasked: from gene variability to future challenges.Frontiers in cellular and infection microbiology · 2025
    Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. The Genomic 3' UTR of Flaviviruses Is a Translation Initiation Enhancer.International journal of molecular sciences · 2022
    Article
  16. Recent advances in RNA structurome.Science China. Life sciences · 2022
    Review
  17. Article
  18. Article
  19. Review
  20. Review

12 more citing papers are in PubMed but not listed here.

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

7 authors at 4 institutions in 1 country.

Mark ManzanoDepartment of Microbiology and Immunology, Georgetown University School of Medicine, Washington, D C 20057, USA.
Erin D Reichert
Stephanie Polo
Barry Falgout
Wojciech Kasprzak
Bruce A Shapiro
Radhakrishnan Padmanabhan
Georgetown University · USCenter for Biologics Evaluation and Research · USNational Institutes of Health · USScience Applications International Corporation (United States) · US

Funding

Computational Approaches for RNA StructureFunction DeterminationZIABC008382 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SHAPIRO, BRUCE · 2009 to 2021
$5.8M
Identification and Analysis of Flavivirus Protease and RNA Helicase InhibitorsR01AI070791 · NIAID · GEORGETOWN UNIVERSITY · PI PADMANABHAN, RADHAKRISHNAN · 2006 to 2009
$1.1M
Dengue and West Nile Viral Protease InhibitorsR21AI057705 · NIAID · GEORGETOWN UNIVERSITY · PI PADMANABHAN, RADHAKRISHNAN · 2004 to 2005
$397k
CCR NIH HHS HHSN261200800001CIntramural NIH HHSNCI NIH HHS HHSN261200800001ENCI NIH HHS N01 CO012400NCI NIH HHS N01-CO-12400NIAID NIH HHS AI 57705NIAID NIH HHS AI 70791NIAID NIH HHS R01 AI070791NIAID NIH HHS R21 AI057705
6 · The paper itself

Abstract

Using the massively parallel genetic algorithm for RNA folding, we show that the core region of the 3'-untranslated region of the dengue virus (DENV) RNA can form two dumbbell structures (5'- and 3'-DBs) of unequal frequencies of occurrence. These structures have the propensity to form two potential pseudoknots between identical five-nucleotide terminal loops 1 and 2 (TL1 and TL2) and their complementary pseudoknot motifs, PK2 and PK1. Mutagenesis using a DENV2 replicon RNA encoding the Renilla luciferase reporter indicated that all four motifs and the conserved sequence 2 (CS2) element within the 3'-DB are important for replication. However, for translation, mutation of TL1 alone does not have any effect; TL2 mutation has only a modest effect in translation, but translation is reduced by ∼60% in the TL1/TL2 double mutant, indicating that TL1 exhibits a cooperative synergy with TL2 in translation. Despite the variable contributions of individual TL and PK motifs in translation, WT levels are achieved when the complementarity between TL1/PK2 and TL2/PK1 is maintained even under conditions of inhibition of the translation initiation factor 4E function mediated by LY294002 via a noncanonical pathway. Taken together, our results indicate that the cis-acting RNA elements in the core region of DENV2 RNA that include two DB structures are required not only for RNA replication but also for optimal translation.

Indexed as

3' Untranslated RegionsAlgorithmsBase SequenceCell LineConserved SequenceDengue VirusLuciferases, RenillaMolecular Sequence DataNucleic Acid ConformationProtein BiosynthesisRegulatory Sequences, Ribonucleic AcidRepliconRNA, ViralVirus Replication3' Untranslated RegionsLuciferases, RenillaRegulatory Sequences, Ribonucleic AcidRNA, Viral

Identifiers

PMID21515677
PMCPMC3121397
OpenAlexW2057093156

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.