| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print December 9, 2002
INSERM U511, Paris 75013
Corresponding Author: vaquero{at}idf.ext.jussieu.fr
TRBP (TAR RNA Binding Protein) and PKR, the interferon-induced dsRNA-regulated protein kinase, contain two dsRNA binding domains in their N-terminus. They both bind to the transactivation response element (TAR) of HIV-1 RNAs through different sites. Binding to dsRNA activates PKR leading to eIF-2a phosphorylation and protein synthesis inhibition. TRBP and PKR can heterodimerize, which inhibits the kinase function of PKR and has a positive effect on HIV-1 expression. In this study, an in vitro reticulocyte assay revealed the poor expression of TAR containing CAT RNAs compared to CAT RNAs. Addition of TRBP restored translation efficiency of TAR-CAT RNA and decreased the phosphorylation status of eIF-2a. Unexpectedly, eIF-2a was phosphorylated in the presence of TAR CAT as well as CAT RNA. TRBP inhibited eIF-2a phosphorylation in both cases, suggesting that it restores the translation of TAR-CAT RNA independently to its ability to inhibit PKR. TRBP activity was then analyzed in a PKR-free environment using PKR-deficient murine embryo fibroblasts. In a transient reporter gene assay, TRBP stimulated the expression of a TAR containing luciferase 3.8 fold whereas mutated TAR structures or devoid of TAR were stimulated 1.5 to 2.4 fold. Overall, the activity of TRBP2 was higher when the 5' end of the mRNA was structured. Increasing concentrations of TRBP showed no significant modification of the luciferase RNA levels, suggesting that TRBP stimulates translation of TAR-containing RNAs. Therefore, TRBP acts as an important cellular factor for efficient translation of dsRNA containing transcripts, both by inhibiting PKR and in a PKR-independent pathway.
J. Biol. Chem, 10.1074/jbc.M208954200
Submitted on September 3, 2002
Revised on December 4, 2002
Accepted on December 9, 2002
The TAR-RNA binding protein, TRBP, stimulates the expression of TAR-containing RNAs in vitro and in vivo independently of its ability to inhibit the dsRNA dependent kinase PKR
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Gendron, J. Charbonneau, D. Dulude, N. Heveker, G. Ferbeyre, and L. Brakier-Gingras The presence of the TAR RNA structure alters the programmed -1 ribosomal frameshift efficiency of the human immunodeficiency virus type 1 (HIV-1) by modifying the rate of translation initiation Nucleic Acids Res., January 17, 2008; 36(1): 30 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Carroll-Anzinger, A. Kumar, V. Adarichev, F. Kashanchi, and L. Al-Harthi Human Immunodeficiency Virus-Restricted Replication in Astrocytes and the Ability of Gamma Interferon To Modulate This Restriction Are Regulated by a Downstream Effector of the Wnt Signaling Pathway J. Virol., June 1, 2007; 81(11): 5864 - 5871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Christensen, A. Daher, K. J. Soye, L. B. Frankel, M. R. Alexander, S. Laine, S. Bannwarth, C. L. Ong, S. W. L. Chung, S. M. Campbell, et al. Small Interfering RNAs against the TAR RNA Binding Protein, TRBP, a Dicer Cofactor, Inhibit Human Immunodeficiency Virus Type 1 Long Terminal Repeat Expression and Viral Production J. Virol., May 15, 2007; 81(10): 5121 - 5131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Garcia, J. Gil, I. Ventoso, S. Guerra, E. Domingo, C. Rivas, and M. Esteban Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action Microbiol. Mol. Biol. Rev., December 1, 2006; 70(4): 1032 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Ong, J. C. Thorpe, P. R. Gorry, S. Bannwarth, A. Jaworowski, J. L. Howard, S. Chung, S. Campbell, H. S. Christensen, G. Clerzius, et al. Low TRBP Levels Support an Innate Human Immunodeficiency Virus Type 1 Resistance in Astrocytes by Enhancing the PKR Antiviral Response J. Virol., October 15, 2005; 79(20): 12763 - 12772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dugre-Brisson, G. Elvira, K. Boulay, L. Chatel-Chaix, A. J. Mouland, and L. DesGroseillers Interaction of Staufen1 with the 5' end of mRNA facilitates translation of these RNAs Nucleic Acids Res., August 26, 2005; 33(15): 4797 - 4812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-S. Chen, F. Tassone, P. Sahota, and P. J. Hagerman The (CGG)n repeat element within the 5' untranslated region of the FMR1 message provides both positive and negative cis effects on in vivo translation of a downstream reporter Hum. Mol. Genet., December 1, 2003; 12(23): 3067 - 3074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kulinski, M. Olejniczak, H. Huthoff, L. Bielecki, K. Pachulska-Wieczorek, A. T. Das, B. Berkhout, and R. W. Adamiak The Apical Loop of the HIV-1 TAR RNA Hairpin Is Stabilized by a Cross-loop Base Pair J. Biol. Chem., October 3, 2003; 278(40): 38892 - 38901. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
