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Journal of Virology, September 2001, p. 8547-8555, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8547-8555.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Hepatitis Delta Virus Minimal Substrates Competent for Editing by ADAR1 and ADAR2

Shuji Sato,1 Swee Kee Wong,1,2 and David W. Lazinski1,2,*

Department of Molecular Biology and Microbiology1 and the Raymond and Beverly Sackler Research Foundation Laboratory, Sackler School of Graduate Biomedical Sciences,2 Tufts University School of Medicine, Boston, Massachusetts 02111

Received 12 April 2001/Accepted 5 June 2001

A host-mediated RNA-editing event allows hepatitis delta virus (HDV) to express two essential proteins, the small delta antigen (HDAg-S) and the large delta antigen (HDAg-L), from a single open reading frame. One or several members of the ADAR (adenosine deaminases that act on RNA) family are thought to convert the adenosine to an inosine (I) within the HDAg-S amber codon in antigenomic RNA. As a consequence of replication, the UIG codon is converted to a UGG (tryptophan [W]) codon in the resulting HDAg-L message. Here, we used a novel reporter system to monitor the editing of the HDV amber/W site in the absence of replication. In cultured cells, we observed that both human ADAR1 (hADAR1) and hADAR2 were capable of editing the amber/W site with comparable efficiencies. We also defined the minimal HDV substrate required for hADAR1- and hADAR2-mediated editing. Only 24 nucleotides from the amber/W site were sufficient to enable efficient editing by hADAR1. Hence, the HDV amber/W site represents the smallest ADAR substrate yet identified. In contrast, the minimal substrate competent for hADAR2-mediated editing contained 66 nucleotides.


* Corresponding author. Mailing address: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111-1817. Phone: (617) 636-3671. Fax: (617) 636-0337. E-mail: david.lazinski{at}tufts.edu.


Journal of Virology, September 2001, p. 8547-8555, Vol. 75, No. 18
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.18.8547-8555.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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