This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aparicio, O.
Right arrow Articles by Fortes, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aparicio, O.
Right arrow Articles by Fortes, P.

 Previous Article  |  Next Article 

Journal of Virology, February 2006, p. 1376-1384, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1376-1384.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Adenovirus Virus-Associated RNA Is Processed to Functional Interfering RNAs Involved in Virus Production

Oscar Aparicio, Nerea Razquin, Mikel Zaratiegui,{ddagger} Iñigo Narvaiza,§ and Puri Fortes*

Division of Gene Therapy and Hepatology, CIMA, University of Navarra, Pio XII 55. 31008, Pamplona, Spain

Received 14 July 2005/ Accepted 12 November 2005

Posttranscriptional gene silencing allows sequence-specific control of gene expression. Specificity is guaranteed by small antisense RNAs such as microRNAs (miRNAs) or small interfering RNAs (siRNAs). Functional miRNAs derive from longer double-stranded RNA (dsRNA) molecules that are cleaved to pre-miRNAs in the nucleus and are transported by exportin 5 (Exp 5) to the cytoplasm. Adenovirus-infected cells express virus-associated (VA) RNAs, which are dsRNA molecules similar in structure to pre-miRNAs. VA RNAs are also transported by Exp 5 to the cytoplasm, where they accumulate. Here we show that small RNAs derived from VA RNAs (svaRNAs), similar to miRNAs, can be found in adenovirus-infected cells. VA RNA processing to svaRNAs requires neither viral replication nor viral protein expression, as evidenced by the fact that svaRNA accumulation can be detected in cells transfected with VA sequences. svaRNAs are efficiently bound by Argonaute 2, the endonuclease of the RNA-induced silencing complex, and behave as functional siRNAs, in that they inhibit the expression of reporter genes with complementary sequences. Blocking svaRNA-mediated inhibition affects efficient adenovirus production, indicating that svaRNAs are required for virus viability. Thus, svaRNA-mediated silencing could represent a novel mechanism used by adenoviruses to control cellular or viral gene expression.

* Corresponding author: Mailing address: Division of Gene Therapy and Hepatology, CIMA, University of Navarra, Pio XII 55, 31008 Pamplona, Spain. Phone: 34-948-194700. Fax: 34-948-194717. E-mail: pfortes{at}unav.es.

{ddagger} Present address: Cold Spring Harbor Laboratory, 1 Bungtown Rd., Cold Spring Harbor, NY 11724.

§ Present address: Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037.

Journal of Virology, February 2006, p. 1376-1384, Vol. 80, No. 3
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.3.1376-1384.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Aparicio, O., Carnero, E., Abad, X., Razquin, N., Guruceaga, E., Segura, V., Fortes, P. (2010). Adenovirus VA RNA-derived miRNAs target cellular genes involved in cell growth, gene expression and DNA repair. Nucleic Acids Res 38: 750-763 [Abstract] [Full Text]  
  • Lam, Y. W., Evans, V. C., Heesom, K. J., Lamond, A. I., Matthews, D. A. (2010). Proteomics Analysis of the Nucleolus in Adenovirus-infected Cells. Mol. Cell. Proteomics 9: 117-130 [Abstract] [Full Text]  
  • Kato, Y., Sawata, S. Y., Inoue, A. (2010). A lentiviral vector encoding two fluorescent proteins enables imaging of adenoviral infection via adenovirus-encoded miRNAs in single living cells. J Biochem 147: 63-71 [Abstract] [Full Text]  
  • Xu, N., Gkountela, S., Saeed, K., Akusjarvi, G. (2009). The 5'-end heterogeneity of adenovirus virus-associated RNAI contributes to the asymmetric guide strand incorporation into the RNA-induced silencing complex. Nucleic Acids Res 37: 6950-6959 [Abstract] [Full Text]  
  • Umbach, J. L., Cullen, B. R. (2009). The role of RNAi and microRNAs in animal virus replication and antiviral immunity. Genes Dev. 23: 1151-1164 [Abstract] [Full Text]  
  • Bandres, E., Bitarte, N., Arias, F., Agorreta, J., Fortes, P., Agirre, X., Zarate, R., Diaz-Gonzalez, J. A., Ramirez, N., Sola, J. J., Jimenez, P., Rodriguez, J., Garcia-Foncillas, J. (2009). microRNA-451 Regulates Macrophage Migration Inhibitory Factor Production and Proliferation of Gastrointestinal Cancer Cells. Clin. Cancer Res. 15: 2281-2290 [Abstract] [Full Text]  
  • Agirre, X., Jimenez-Velasco, A., San Jose-Eneriz, E., Garate, L., Bandres, E., Cordeu, L., Aparicio, O., Saez, B., Navarro, G., Vilas-Zornoza, A., Perez-Roger, I., Garcia-Foncillas, J., Torres, A., Heiniger, A., Calasanz, M. J., Fortes, P., Roman-Gomez, J., Prosper, F. (2008). Down-Regulation of hsa-miR-10a in Chronic Myeloid Leukemia CD34+ Cells Increases USF2-Mediated Cell Growth. Mol Cancer Res 6: 1830-1840 [Abstract] [Full Text]  
  • Abad, X., Vera, M., Jung, S. P., Oswald, E., Romero, I., Amin, V., Fortes, P., Gunderson, S. I. (2008). Requirements for gene silencing mediated by U1 snRNA binding to a target sequence. Nucleic Acids Res 36: 2338-2352 [Abstract] [Full Text]  
  • Dolken, L., Perot, J., Cognat, V., Alioua, A., John, M., Soutschek, J., Ruzsics, Z., Koszinowski, U., Voinnet, O., Pfeffer, S. (2007). Mouse Cytomegalovirus MicroRNAs Dominate the Cellular Small RNA Profile during Lytic Infection and Show Features of Posttranscriptional Regulation. J. Virol. 81: 13771-13782 [Abstract] [Full Text]  
  • Wu, Y., Maruo, S., Yajima, M., Kanda, T., Takada, K. (2007). Epstein-Barr Virus (EBV)-Encoded RNA 2 (EBER2) but Not EBER1 Plays a Critical Role in EBV-Induced B-Cell Growth Transformation. J. Virol. 81: 11236-11245 [Abstract] [Full Text]  
  • Xu, N., Segerman, B., Zhou, X., Akusjarvi, G. (2007). Adenovirus Virus-Associated RNAII-Derived Small RNAs Are Efficiently Incorporated into the RNA-Induced Silencing Complex and Associate with Polyribosomes. J. Virol. 81: 10540-10549 [Abstract] [Full Text]  
  • Narvaiza, I., Aparicio, O., Vera, M., Razquin, N., Bortolanza, S., Prieto, J., Fortes, P. (2006). Effect of Adenovirus-Mediated RNA Interference on Endogenous MicroRNAs in a Mouse Model of Multidrug Resistance Protein 2 Gene Silencing. J. Virol. 80: 12236-12247 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»