Evidence map›Paper›PMID 31186504›Full record

ArticleScientific reports2019

Regulation of the Hepatitis B virus replication and gene expression by the multi-functional protein TARDBP.

Grace Naswa Makokha, Hiromi Abe-Chayama, Sajeda Chowdhury, C Nelson Hayes, Masataka Tsuge, Tadahiko Yoshima, Yuji Ishida, Yizhou Zhang, Takuro Uchida, Chise Tateno and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. TRMT6-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
  4. Article
  5. The host geneActa biochimica et biophysica Sinica · 2024
    Article
  6. Article
  7. Article
  8. Implications of TDP-43 in non-neuronal systems.Cell communication and signaling : CCS · 2023
    Review
  9. Virus Infection and mRNA Nuclear Export.International journal of molecular sciences · 2023
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Grace Naswa MakokhaDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima, Japan.
Hiromi Abe-ChayamaDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima, Japan.
Sajeda ChowdhuryDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima, Japan.
C Nelson HayesDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima, Japan.
Masataka TsugeDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima, Japan.
Tadahiko YoshimaLiver Research Project Center, Hiroshima, Japan.
Yuji IshidaPhoenixBio Co., Ltd., 3-4-1 Kagamiyama, Higashihiroshima, 739-0046, Japan.
Yizhou ZhangDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima, Japan.
Takuro UchidaDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima, Japan.
Chise TatenoPhoenixBio Co., Ltd., 3-4-1 Kagamiyama, Higashihiroshima, 739-0046, Japan.
Rie AkiyamaDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima, Japan.
Kazuaki ChayamaDepartment of Gastroenterology and Metabolism, Institute of Biomedical and Health Science, Hiroshima, Japan. chayama@hiroshima-u.ac.jp.
Hiroshima Prefectural Rehabilitation Center · JPPhoenixBio (Japan) · JPHiroshima University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatitis B virus (HBV) infects the liver and is a key risk factor for hepatocellular carcinoma. Identification of host factors that support viral replication is important to understand mechanisms of viral replication and to develop new therapeutic strategies. We identified TARDBP as a host factor that regulates HBV. Silencing or knocking out the protein in HBV infected cells severely impaired the production of viral replicative intermediates, mRNAs, proteins, and virions, whereas ectopic expression of TARDBP rescued production of these products. Mechanistically, we found that the protein binds to the HBV core promoter, as shown by chromatin precipitation as well as mutagenesis and protein-DNA interaction assays. Using LC-MS/MS analysis, we also found that TARDBP binds to a number of other proteins known to support the HBV life cycle, including NPM1, PARP1, Hsp90, HNRNPC, SFPQ, PTBP1, HNRNPK, and PUF60. Interestingly, given its key role as a regulator of RNA splicing, we found that TARDBP has an inhibitory role on pregenomic RNA splicing, which might help the virus to export its non-canonical RNAs from the nucleus without being subjected to unwanted splicing, even though mRNA nuclear export is normally closely tied to RNA splicing. Taken together, our results demonstrate that TARDBP is involved in multiple steps of HBV replication via binding to both HBV DNA and RNA. The protein's broad interactome suggests that TARDBP may function as part of a RNA-binding scaffold involved in HBV replication and that the interaction between these proteins might be a target for development of anti-HBV drugs.

Indexed as

Gene Expression Regulation, ViralBase SequenceBinding SitesCell NucleusCRISPR-Cas SystemsDNA-Binding ProteinsGene SilencingHepatitis BHepatitis B virusHep G2 CellsHumansNucleophosminPromoter Regions, GeneticRNA Recognition MotifRNA SplicingTranscription, GeneticDNA-Binding ProteinsNPM1 protein, humanNucleophosminTARDBP protein, human

Identifiers

PMID31186504
PMCPMC6560085
OpenAlexW2950943784

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.