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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-11-5
pubmed:abstractText
The RNA-specific adenosine deaminase (ADAR1) is an interferon-inducible editing enzyme that converts adenosine to inosine. ADAR1 contains three distinct domains: a N-terminal Z-DNA binding domain that includes two Z-DNA binding motifs; a central double-stranded RNA binding domain that includes three dsRNA binding motifs (dsRBM); and a C-terminal catalytic domain responsible for A-to-I enzymatic activity. The E3L protein of vaccinia virus mediates interferon resistance. E3L, similar to ADAR1, also contains Z-DNA binding and dsRNA binding motifs. To assess the possible role of E3L in modulating RNA editing by ADAR1, we examined the effect of E3L on ADAR1 deaminase activity. Wild-type E3L protein was a potent inhibitor of ADAR1 deaminase enzymatic activity. Analysis of mutant E3L proteins indicated that the carboxy-proximal dsRBM of E3L was essential for antagonism of ADAR1. Surprisingly, disruption of the Z-DNA binding domain of E3L by double substitutions of two highly conserved residues also abolished its antagonistic activity, whereas deletion of the entire Z domain had little effect on the inhibition. With natural neurotransmitter pre-mRNA substrates, E3L weakly inhibited the site-selective editing activity by ADAR1 at the R/G site of the glutamate receptor B subunit (GluR-B) pre-mRNA and the A site of serotonin 2C receptor (5-HT2CR) pre-mRNA; editing of the intronic hotspot (+)60 site of GluR-B was not affected by E3L. These results demonstrate that the A-to-I RNA editing activity of the IFN-inducible adenosine deaminase is impaired by the product of the vaccinia virus E3L interferon resistance gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0042-6822
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
289
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
378-87
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Vaccinia virus E3L interferon resistance protein inhibits the interferon-induced adenosine deaminase A-to-I editing activity.
pubmed:affiliation
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.