Evidence map›Paper›PMID 12438577›Full record

ArticleJournal of virology2002

Mechanism of de novo initiation by the hepatitis C virus RNA-dependent RNA polymerase: role of divalent metals.

C T Ranjith-Kumar, Young-Chan Kim, Les Gutshall, Carol Silverman, Sanjay Khandekar, Robert T Sarisky, C Cheng Kao

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

43 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Biochemical characterization of the Lassa virus L protein.The Journal of biological chemistry · 2019
    Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Hepatitis C virus RNA replication.Current topics in microbiology and immunology · 2013
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Viral polymerases.Advances in experimental medicine and biology · 2012
    Review
  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

7 authors at 2 institutions in 1 country.

C T Ranjith-KumarDepartment of Biology, Indiana University, 1001 E. Third Street, Bloomington, IN 47405, USA.
Young-Chan Kim
Les Gutshall
Carol Silverman
Sanjay Khandekar
Robert T Sarisky
C Cheng Kao
GlaxoSmithKline (United States) · USIndiana University Bloomington · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We functionally analyzed the role of metal ions in RNA-dependent RNA synthesis by three recombinant RNA-dependent RNA polymerases (RdRps) from GB virus-B (GBV), bovine viral diarrhea virus (BVDV), and hepatitis C virus (HCV), with emphasis on the HCV RdRp. Using templates capable of both de novo initiation and primer extension and RdRps purified in the absence of metal, we found that only reactions with exogenously provided Mg(2+) and Mn(2+) gave rise to significant amounts of synthesis. Mg(2+) and Mn(2+) affected the mode of RNA synthesis by the three RdRps. Both metals supported primer-dependent and de novo-initiated RNA by the GBV RdRp, while Mn(2+) significantly increased the amount of de novo-initiated products by the HCV and BVDV RdRps. For the HCV RdRp, Mn(2+) reduced the K(m) for the initiation nucleotide, a GTP, from 103 to 3 micro M. However, it increased de novo initiation even at GTP concentrations that are comparable to physiological levels. We hypothesize that a change in RdRp structure occurs upon GTP binding to prevent primer extension. Analysis of deleted proteins revealed that the C terminus of the HCV RdRp plays a role in Mn(2+)-induced de novo initiation and can contribute to the suppression of primer extension. Spectroscopy examining the intrinsic fluorescence of tyrosine and tryptophan residues in the HCV RdRp produced results consistent with the protein undergoing a conformational change in the presence of metal. These results document the fact that metal can affect de novo initiation or primer extension by flaviviral RdRps.

Indexed as

Guanosine TriphosphateHepacivirusMagnesiumManganeseRNA-Dependent RNA PolymeraseRNA, ViralSpectrometry, FluorescenceGuanosine TriphosphateMagnesiumManganeseRNA-Dependent RNA PolymeraseRNA, Viral

Identifiers

PMID12438577
PMCPMC136676
OpenAlexW2097857791

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.