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
Services
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 Poulsen, H.
Right arrow Articles by Kjems, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Poulsen, H.
Right arrow Articles by Kjems, J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2001, p. 7862-7871, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7862-7871.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

CRM1 Mediates the Export of ADAR1 through a Nuclear Export Signal within the Z-DNA Binding Domain

Hanne Poulsen, Jakob Nilsson, Christian K. Damgaard, Jan Egebjerg, and Jørgen Kjems*

Department of Molecular and Structural Biology, University of Aarhus, DK-8000 Århus C, Denmark

Received 12 March 2001/Returned for modification 10 July 2001/Accepted 21 August 2001

RNA editing of specific residues by adenosine deamination is a nuclear process catalyzed by adenosine deaminases acting on RNA (ADAR). Different promoters in the ADAR1 gene give rise to two forms of the protein: a constitutive promoter expresses a transcript encoding (c)ADAR1, and an interferon-induced promoter expresses a transcript encoding an N-terminally extended form, (i)ADAR1. Here we show that (c)ADAR1 is primarily nuclear whereas (i)ADAR1 encompasses a functional nuclear export signal in the N-terminal part and is a nucleocytoplasmic shuttle protein. Mutation of the nuclear export signal or treatment with the CRM1-specific drug leptomycin B induces nuclear accumulation of (i)ADAR1 fused to the green fluorescent protein and increases the nuclear editing activity. In concurrence, CRM1 and RanGTP interact specifically with the (i)ADAR1 nuclear export signal to form a tripartite export complex in vitro. Furthermore, our data imply that nuclear import of (i)ADAR1 is mediated by at least two nuclear localization sequences. These results suggest that the nuclear editing activity of (i)ADAR1 is modulated by nuclear export.


* Corresponding author. Mailing address: Department of Molecular and Structural Biology, University of Aarhus, C. F. Møllers Allé, Building 130, DK-8000 Aarhus C, Denmark. Phone: 45 8942 2686. Fax: 45 8619 6500. E-mail: Kjems{at}biobase.dk.


Molecular and Cellular Biology, November 2001, p. 7862-7871, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7862-7871.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Fritz, J., Strehblow, A., Taschner, A., Schopoff, S., Pasierbek, P., Jantsch, M. F. (2009). RNA-Regulated Interaction of Transportin-1 and Exportin-5 with the Double-Stranded RNA-Binding Domain Regulates Nucleocytoplasmic Shuttling of ADAR1. Mol. Cell. Biol. 29: 1487-1497 [Abstract] [Full Text]  
  • Phuphuakrat, A., Kraiwong, R., Boonarkart, C., Lauhakirti, D., Lee, T.-H., Auewarakul, P. (2008). Double-Stranded RNA Adenosine Deaminases Enhance Expression of Human Immunodeficiency Virus Type 1 Proteins. J. Virol. 82: 10864-10872 [Abstract] [Full Text]  
  • Gaston, K. W., Rubio, M. A. T., Spears, J. L., Pastar, I., Papavasiliou, F. N., Alfonzo, J. D. (2007). C to U editing at position 32 of the anticodon loop precedes tRNA 5' leader removal in trypanosomatids. Nucleic Acids Res 35: 6740-6749 [Abstract] [Full Text]  
  • Lykke-Andersen, S., Pinol-Roma, S., Kjems, J. (2007). Alternative splicing of the ADAR1 transcript in a region that functions either as a 5'-UTR or an ORF. RNA 13: 1732-1744 [Abstract] [Full Text]  
  • Poulsen, H., Jorgensen, R., Heding, A., Nielsen, F. C., Bonven, B., Egebjerg, J. (2006). Dimerization of ADAR2 is mediated by the double-stranded RNA binding domain. RNA 12: 1350-1360 [Abstract] [Full Text]  
  • Desterro, J. M.P., Keegan, L. P., Jaffray, E., Hay, R. T., O'Connell, M. A., Carmo-Fonseca, M. (2005). SUMO-1 Modification Alters ADAR1 Editing Activity. Mol. Biol. Cell 16: 5115-5126 [Abstract] [Full Text]  
  • George, C. X., Wagner, M. V., Samuel, C. E. (2005). Expression of Interferon-inducible RNA Adenosine Deaminase ADAR1 during Pathogen Infection and Mouse Embryo Development Involves Tissue-selective Promoter Utilization and Alternative Splicing. J. Biol. Chem. 280: 15020-15028 [Abstract] [Full Text]  
  • Yang, W., Wang, Q., Howell, K. L., Lee, J. T., Cho, D.-S. C., Murray, J. M., Nishikura, K. (2005). ADAR1 RNA Deaminase Limits Short Interfering RNA Efficacy in Mammalian Cells. J. Biol. Chem. 280: 3946-3953 [Abstract] [Full Text]  
  • Wang, Q., Carmichael, G. G. (2004). Effects of Length and Location on the Cellular Response to Double-Stranded RNA. Microbiol. Mol. Biol. Rev. 68: 432-452 [Abstract] [Full Text]  
  • Nie, Y., Zhao, Q., Su, Y., Yang, J.-H. (2004). Subcellular Distribution of ADAR1 Isoforms Is Synergistically Determined by Three Nuclear Discrimination Signals and a Regulatory Motif. J. Biol. Chem. 279: 13249-13255 [Abstract] [Full Text]  
  • Yang, J.-H., Nie, Y., Zhao, Q., Su, Y., Pypaert, M., Su, H., Rabinovici, R. (2003). Intracellular Localization of Differentially Regulated RNA-specific Adenosine Deaminase Isoforms in Inflammation. J. Biol. Chem. 278: 45833-45842 [Abstract] [Full Text]  
  • Kim, Y.-G., Muralinath, M., Brandt, T., Pearcy, M., Hauns, K., Lowenhaupt, K., Jacobs, B. L., Rich, A. (2003). A role for Z-DNA binding in vaccinia virus pathogenesis. Proc. Natl. Acad. Sci. USA 100: 6974-6979 [Abstract] [Full Text]  
  • Cho, D.-S. C., Yang, W., Lee, J. T., Shiekhattar, R., Murray, J. M., Nishikura, K. (2003). Requirement of Dimerization for RNA Editing Activity of Adenosine Deaminases Acting on RNA. J. Biol. Chem. 278: 17093-17102 [Abstract] [Full Text]  
  • WONG, S. K., SATO, S., LAZINSKI, D. W. (2003). Elevated activity of the large form of ADAR1 in vivo: Very efficient RNA editing occurs in the cytoplasm. RNA 9: 586-598 [Abstract] [Full Text]  
  • Desterro, J. M. P., Keegan, L. P., Lafarga, M., Berciano, M. T., O'Connell, M., Carmo-Fonseca, M. (2003). Dynamic association of RNA-editing enzymes with the nucleolus. J. Cell Sci. 116: 1805-1818 [Abstract] [Full Text]  
  • Maas, S., Rich, A., Nishikura, K. (2003). A-to-I RNA Editing: Recent News and Residual Mysteries. J. Biol. Chem. 278: 1391-1394 [Full Text]  
  • Wong, S. K., Lazinski, D. W. (2002). Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1. Proc. Natl. Acad. Sci. USA 99: 15118-15123 [Abstract] [Full Text]  
  • Strehblow, A., Hallegger, M., Jantsch, M. F. (2002). Nucleocytoplasmic Distribution of Human RNA-editing Enzyme ADAR1 Is Modulated by Double-stranded RNA-binding Domains, a Leucine-rich Export Signal, and a Putative Dimerization Domain. Mol. Biol. Cell 13: 3822-3835 [Abstract] [Full Text]