HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 15, 15020-15028, April 15, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/15/15020    most recent M500476200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by George, C. X. Articles by Samuel, C. E. Search for Related Content PubMed PubMed Citation Articles by George, C. X. Articles by Samuel, C. E. Social Bookmarking                      What's this?

Expression of Interferon-inducible RNA Adenosine Deaminase ADAR1 during Pathogen Infection and Mouse Embryo Development Involves Tissue-selective Promoter Utilization and Alternative Splicing^*

Cyril X. George, Michelle V. Wagner, and Charles E. Samuel

From the Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106

ADAR1 (adenosine deaminase acting on RNA) is widely expressed in adult mammals and has a critical role during embryogenesis. Two size forms of ADAR1 are known that possess adenosine-to-inosine editing activity: an interferon (IFN)-inducible 150-kDa protein and a constitutively expressed N-terminally truncated 110-kDa protein. We defined the structure of the 5'-flanking region of the mouse Adar1 gene, and we show here that mouse Adar1 transcripts possess alternative exon 1 structures (1A, 1B, and 1C) that initiate from unique promoters and are spliced to a common exon 2 junction. Exon 1A-containing transcripts encoding p150 were expressed in all tissues examined from adult mice (brain, cecum, heart, kidney, liver, lung, spleen, and Peyer's patches) and were elevated most significantly in liver but remained lowest in brain following oral infection with Salmonella. Exon 1B-containing RNA was most abundant in brain and was not increased in any tissue examined following infection. Exon 1C-containing RNA was very scarce. Exon 1A, but not exon 1B or 1C, expression was increased in fibroblast L cells treated with IFN, and a consensus ISRE element was present in the promoter driving exon 1A expression. Exon 1B, but not 1A, was detectable in embryonic day 10.5 embryos and was abundantly expressed in embryonic day 15 embryos. Furthermore, the ADAR1 p110 protein isoform was detected in embryonic tissue, whereas both p110 and the inducible p150 proteins were found in IFN-treated L cells. Finally, the presence of alternative exon 7a correlated with exon 1B-containing RNA, and alternative exon 7b correlated with exon 1A-containing RNA. These results establish that multiple promoters drive the expression of the Adar1 gene in adult mice, that the IFN inducible promoter and exon 1A-containing RNA are primarily responsible for the increased ADAR1 observed in Salmonella-infected mice, and that the constitutive exon 1B-containing transcript and encoded p110 protein product are abundantly expressed both in adult brain and during embryogenesis.

Received for publication, January 14, 2005

^* This work was supported in part by Grant AI-12520 from the NIAID, National Institutes of Health, U.S. Public Health Service. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the DDBJ/GenBank^TM/EBI Data Bank with accession number(s) AY488121–AY488123, AY508955–AY508958, AY509125, and AY509126.

To whom correspondence should be addressed. Tel.: 805-893-3097; E-mail: samuel{at}lifesci.ucsb.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Simon, D. M. Heithoff, M. J. Mahan, and C. E. Samuel Comparison of Tissue-Selective Proinflammatory Gene Induction in Mice Infected with Wild-Type, DNA Adenine Methylase-Deficient, and Flagellin-Deficient Salmonella enterica Infect. Immun., December 1, 2007; 75(12): 5627 - 5639. [Abstract] [Full Text] [PDF]

				S. Lykke-Andersen, S. Pinol-Roma, and J. Kjems Alternative splicing of the ADAR1 transcript in a region that functions either as a 5'-UTR or an ORF RNA, October 1, 2007; 13(10): 1732 - 1744. [Abstract] [Full Text] [PDF]

				M. F. Mehler and J. S. Mattick Noncoding RNAs and RNA Editing in Brain Development, Functional Diversification, and Neurological Disease Physiol Rev, July 1, 2007; 87(3): 799 - 823. [Abstract] [Full Text] [PDF]

				J.-P. Levraud, P. Boudinot, I. Colin, A. Benmansour, N. Peyrieras, P. Herbomel, and G. Lutfalla Identification of the Zebrafish IFN Receptor: Implications for the Origin of the Vertebrate IFN System J. Immunol., April 1, 2007; 178(7): 4385 - 4394. [Abstract] [Full Text] [PDF]

				B. R. tenOever, S.-L. Ng, M. A. Chua, S. M. McWhirter, A. Garcia-Sastre, and T. Maniatis Multiple Functions of the IKK-Related Kinase IKK{epsilon} in Interferon-Mediated Antiviral Immunity Science, March 2, 2007; 315(5816): 1274 - 1278. [Abstract] [Full Text] [PDF]

				R. C. Zahn, I. Schelp, O. Utermohlen, and D. von Laer A-to-G Hypermutation in the Genome of Lymphocytic Choriomeningitis Virus J. Virol., January 15, 2007; 81(2): 457 - 464. [Abstract] [Full Text] [PDF]

				Z. Gan, L. Zhao, L. Yang, P. Huang, F. Zhao, W. Li, and Y. Liu RNA Editing by ADAR2 Is Metabolically Regulated in Pancreatic Islets and beta-Cells J. Biol. Chem., November 3, 2006; 281(44): 33386 - 33394. [Abstract] [Full Text] [PDF]