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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.


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