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The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation initiation at the rhinovirus type 2 internal ribosome entry site.

Publication ,  Journal Article
Merrill, MK; Gromeier, M
Published in: J Virol
July 2006

Poliovirus (PV) plus-strand RNA genomes initiate translation in a cap-independent manner via an internal ribosome entry site (IRES) in their 5' untranslated region. Viral translation is codetermined by cellular IRES trans-acting factors, which can influence viral propagation in a cell-type-specific manner. Engineering of a poliovirus recombinant devoid of neuropathogenic properties but highly lytic in malignant glioma cells was accomplished by exchange of the cognate poliovirus IRES with its counterpart from human rhinovirus type 2 (HRV2), generating PV-RIPO. Neuroblast:glioma heterokaryon analyses revealed that loss of neurovirulence is due to trans-dominant repression of PV-RIPO propagation in neuronal cells. The double-stranded RNA binding protein 76 (DRBP76) was previously identified to bind to the HRV2 IRES in neuronal cells and to inhibit PV-RIPO translation and propagation (M. Merrill, E. Dobrikova, and M. Gromeier, J. Virol. 80:3347-3356, 2006). The results of size exclusion chromatography indicate that DRBP76 heterodimerizes with nuclear factor of activated T cells, 45 kDa (NF45), in neuronal but not in glioma cells. The DRBP76:NF45 heterodimer binds to the HRV2 IRES in neuronal but not in glioma cells. Ribosomal profile analyses show that the heterodimer preferentially associates with the translation apparatus in neuronal cells and arrests translation at the HRV2 IRES, preventing PV-RIPO RNA assembly into polysomes. Results of this study suggest that the DRBP76:NF45 heterodimer selectively blocks HRV2 IRES-driven translation initiation in neuron-derived cells.

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

July 2006

Volume

80

Issue

14

Start / End Page

6936 / 6942

Location

United States

Related Subject Headings

  • Virology
  • Rhinovirus
  • RNA-Binding Proteins
  • RNA, Viral
  • RNA, Double-Stranded
  • Protein Biosynthesis
  • Protein Binding
  • Polyribosomes
  • Organ Specificity
  • Nuclear Factor 45 Protein
 

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Merrill, M. K., & Gromeier, M. (2006). The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation initiation at the rhinovirus type 2 internal ribosome entry site. J Virol, 80(14), 6936–6942. https://doi.org/10.1128/JVI.00243-06
Merrill, Melinda K., and Matthias Gromeier. “The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation initiation at the rhinovirus type 2 internal ribosome entry site.J Virol 80, no. 14 (July 2006): 6936–42. https://doi.org/10.1128/JVI.00243-06.
Merrill, Melinda K., and Matthias Gromeier. “The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation initiation at the rhinovirus type 2 internal ribosome entry site.J Virol, vol. 80, no. 14, July 2006, pp. 6936–42. Pubmed, doi:10.1128/JVI.00243-06.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

July 2006

Volume

80

Issue

14

Start / End Page

6936 / 6942

Location

United States

Related Subject Headings

  • Virology
  • Rhinovirus
  • RNA-Binding Proteins
  • RNA, Viral
  • RNA, Double-Stranded
  • Protein Biosynthesis
  • Protein Binding
  • Polyribosomes
  • Organ Specificity
  • Nuclear Factor 45 Protein