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Molecular and Cellular Biology, August 2005, p. 6956-6963, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.6956-6963.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

ADAR1 Interacts with NF90 through Double-Stranded RNA and Regulates NF90-Mediated Gene Expression Independently of RNA Editing

Yongzhan Nie,¹ Li Ding,^1, Peter N. Kao,² Robert Braun,³ and Jing-Hua Yang^1*

Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520,¹ Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California 94305-5236,² Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195³

Received 5 January 2005/ Returned for modification 10 March 2005/ Accepted 16 May 2005

The RNA-editing enzyme ADAR1 modifies adenosines by deamination and produces A-to-I mutations in mRNA. ADAR1 was recently demonstrated to function in host defense and in embryonic erythropoiesis during fetal liver development. The mechanisms for these phenotypic effects are not yet known. Here we report a novel function of ADAR1 in the regulation of gene expression by interacting with the nuclear factor 90 (NF90) proteins, known regulators that bind the antigen response recognition element (ARRE-2) and have been demonstrated to stimulate transcription and translation. ADAR1 upregulates NF90-mediated gene expression by interacting with the NF90 proteins, including NF110, NF90, and NF45. A knockdown of NF90 with small interfering RNA suppresses this function of ADAR1. Coimmunoprecipitation and double-stranded RNA (dsRNA) digestion demonstrate that ADAR1 is associated with NF110, NF90, and NF45 through the bridge of cellular dsRNA. Studies with ADAR1 deletions demonstrate that the dsRNA binding domain and a region covering the Z-DNA binding domain and the nuclear export signal comprise the complete function of ADAR1 in upregulating NF90-mediated gene expression. These data suggest that ADAR1 has the potential both to change information content through editing of mRNA and to regulate gene expression through interacting with the NF90 family proteins.

Present address: Xian International Medical Research Institute, Shaanxi, People’s Republic of China.

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