ArticleJournal of virology2005
A peptide derived from RNA recognition motif 2 of human la protein binds to hepatitis C virus internal ribosome entry site, prevents ribosomal assembly, and inhibits internal initiation of translation.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Structure-based virtual screening of unbiased and RNA-focused libraries to identify new ligands for the HCV IRES model system.RSC medicinal chemistry · 2024Article
- La proteins couple use of sequence-specific and non-specific binding modes to engage RNA substrates.RNA biology · 2021Review
- Enteroviruses: Classification, Diseases They Cause, and Approaches to Development of Antiviral Drugs.Biochemistry. Biokhimiia · 2017Review
- Catalytic metallodrugs based on the LaR2C peptide target HCV SLIV IRES RNA.Dalton transactions (Cambridge, England : 2003) · 2015Article
- Exploring Internal Ribosome Entry Sites as Therapeutic Targets.Frontiers in oncology · 2015Review
- Specific sequence of a Beta turn in human la protein may contribute to species specificity of hepatitis C virus.Journal of virology · 2014Article
- Hepatitis C virus translation inhibitors targeting the internal ribosomal entry site.Journal of medicinal chemistry · 2014Review
- Targeting ribosome assembly on the HCV RNA using a small RNA molecule.RNA biology · 2012Article
- A La autoantigen homologue is required for the internal ribosome entry site mediated translation of giardiavirus.PloS one · 2011Article
- Proanthocyanidin from blueberry leaves suppresses expression of subgenomic hepatitis C virus RNA.The Journal of biological chemistry · 2009Article
- Structural determinant of human La protein critical for internal initiation of translation of hepatitis C virus RNA.Journal of virology · 2008Article
- Mouse and human La proteins differ in kinase substrate activity and activation mechanism for tRNA processing.Gene expression · 2007Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human La protein is known to interact with hepatitis C virus (HCV) internal ribosome entry site (IRES) and stimulate translation. Previously, we demonstrated that mutations within HCV SL IV lead to reduced binding to La-RNA recognition motif 2 (RRM2) and drastically affect HCV IRES-mediated translation. Also, the binding of La protein to SL IV of HCV IRES was shown to impart conformational alterations within the RNA so as to facilitate the formation of functional initiation complex. Here, we report that a synthetic peptide, LaR2C, derived from the C terminus of La-RRM2 competes with the binding of cellular La protein to the HCV IRES and acts as a dominant negative inhibitor of internal initiation of translation of HCV RNA. The peptide binds to the HCV IRES and inhibits the functional initiation complex formation. An Huh7 cell line constitutively expressing a bicistronic RNA in which both cap-dependent and HCV IRES-mediated translation can be easily assayed has been developed. The addition of purified TAT-LaR2C recombinant polypeptide that allows direct delivery of the peptide into the cells showed reduced expression of HCV IRES activity in this cell line. The study reveals valuable insights into the role of La protein in ribosome assembly at the HCV IRES and also provides the basis for targeting ribosome-HCV IRES interaction to design potent antiviral therapy.
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Registered trials
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.