Evidence map›Paper›PMID 24970889›Full record

ArticleThe Journal of biological chemistry2014

Dissection of the adenoviral VA RNAI central domain structure reveals minimum requirements for RNA-mediated inhibition of PKR.

Jo L Wilson, Virginia K Vachon, S Sunita, Samantha L Schwartz, Graeme L Conn

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

14 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Structural Insights into Human Adenovirus Type 4 Virus-Associated RNA I.International journal of molecular sciences · 2022
    Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Viral noncoding RNAs: more surprises.Genes & development · 2015
    Review
  14. 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

5 authors at 1 institution in 1 country.

Jo L WilsonDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
Virginia K VachonDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
S SunitaDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
Samantha L SchwartzDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322.
Graeme L ConnDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322. Electronic address: gconn@emory.edu.
Emory University · US

Funding

Structural studies of PKR regulation by viral non-coding RNAR21AI097803 · NIAID · EMORY UNIVERSITY · PI CONN, GRAEME L · 2012 to 2013
$391k
NIAID NIH HHS R21 AI097803NIAID NIH HHS R21-AI097803
6 · The paper itself

Abstract

Virus-associated RNA I (VA RNAI) is a short (∼160-nucleotide) non-coding RNA transcript employed by adenoviruses to subvert the innate immune system protein double-stranded RNA-activated protein kinase (PKR). The central domain of VA RNAI is proposed to contain a complex tertiary structure that contributes to its optimal inhibitory activity against PKR. Here we use a combination of VA RNAI mutagenesis, structural analyses, as well as PKR activity and binding assays to dissect this tertiary structure and assess its functional role. Our results support the existence of a pH- and Mg(2+)-dependent tertiary structure involving pseudoknot formation within the central domain. Unexpectedly, this structure appears to play no direct role in PKR inhibition. Deletion of central domain sequences within a minimal but fully active construct lacking the tertiary structure reveals a crucial role in PKR binding and inhibition for nucleotides in the 5' half of the central domain. Deletion of the central domain 3' half also significantly impacts activity but appears to arise indirectly by reducing its capacity to assist in optimally presenting the 5' half sequence. Collectively, our results identify regions of VA RNAI critical for PKR inhibition and reveal that the requirements for an effective RNA inhibitor of PKR are simpler than appreciated previously.

Indexed as

Nucleic Acid ConformationAdenoviridaeeIF-2 KinaseHydrogen-Ion ConcentrationMagnesiumMutagenesisRNA, Viraladenovirus associated RNAeIF-2 KinaseMagnesiumRNA, ViralAdenovirusIsothermal Titration Calorimetry (ITC)MutagenesisProtein Kinase RNA-activated (PKR)RNA-Protein InteractionRNA StructureSHAPE Structure ProbingTranslation ControlUV Melting

Identifiers

PMID24970889
PMCPMC4132820
OpenAlexW2043129552

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.