Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
The human but not the Xenopus RNA-editing enzyme ADAR1 has an atypical nuclear localization signal and displays the characteristics of a shuttling protein.
Eckmann CR
,
Neunteufl A
,
Pfaffstetter L
,
Jantsch MF
.
???displayArticle.abstract???
The RNA-editing enzyme ADAR1 (adenosine deaminase that acts on RNA) is a bona fide nuclear enzyme that has been cloned from several vertebrate species. Putative nuclear localization signals (NLSs) have been identified in the aminoterminal regions of both human and Xenopus ADAR1. Here we show that neither of these predicted NLSs is biologically active. Instead, we could identify a short basic region located upstream of the RNA-binding domains of Xenopus ADAR1 to be necessary and sufficient for nuclear import. In contrast, the homologous region in human ADAR1 does not display NLS activity. Instead, we could map an NLS in human ADAR1 that overlaps with its third double-stranded RNA-binding domain. Interestingly, the NLS activity displayed by this double-stranded RNA-binding domain does not depend on RNA binding, therefore showing a dual function for this domain. Furthermore, nuclear accumulation of human (hs) ADAR1 is transcription dependent and can be stimulated by LMB, an inhibitor of Crm1-dependent nuclear export, indicating that hsADAR1 can move between the nucleus and cytoplasm. Regulated nuclear import and export of hsADAR1 can provide an excellent mechanism to control nuclear concentration of this editing enzyme thereby preventing hyperediting of structured nuclear RNAs.
Aruscavage,
A phylogenetic analysis reveals an unusual sequence conservation within introns involved in RNA editing.
2000, Pubmed
Aruscavage,
A phylogenetic analysis reveals an unusual sequence conservation within introns involved in RNA editing.
2000,
Pubmed
Bass,
A developmentally regulated activity that unwinds RNA duplexes.
1987,
Pubmed
,
Xenbase
Bass,
RNA editing and hypermutation by adenosine deamination.
1997,
Pubmed
Brooks,
The double-stranded RNA-binding domains of Xenopus laevis ADAR1 exhibit different RNA-binding behaviors.
1998,
Pubmed
,
Xenbase
Brusa,
Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice.
1995,
Pubmed
Burns,
Regulation of serotonin-2C receptor G-protein coupling by RNA editing.
1997,
Pubmed
Bycroft,
NMR solution structure of a dsRNA binding domain from Drosophila staufen protein reveals homology to the N-terminal domain of ribosomal protein S5.
1995,
Pubmed
Chen,
A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains.
2000,
Pubmed
Dingwall,
Nuclear targeting sequences--a consensus?
1991,
Pubmed
Eckmann,
The RNA-editing enzyme ADAR1 is localized to the nascent ribonucleoprotein matrix on Xenopus lampbrush chromosomes but specifically associates with an atypical loop.
1999,
Pubmed
,
Xenbase
Evan,
Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
1985,
Pubmed
,
Xenbase
Fornerod,
CRM1 is an export receptor for leucine-rich nuclear export signals.
1997,
Pubmed
,
Xenbase
George,
Characterization of the 5'-flanking region of the human RNA-specific adenosine deaminase ADAR1 gene and identification of an interferon-inducible ADAR1 promoter.
1999,
Pubmed
Herb,
Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences.
1996,
Pubmed
Herbert,
A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase.
1997,
Pubmed
Herbert,
The Zalpha domain from human ADAR1 binds to the Z-DNA conformer of many different sequences.
1998,
Pubmed
Higuchi,
Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2.
2000,
Pubmed
Hodel,
Dissection of a nuclear localization signal.
2001,
Pubmed
Hough,
Analysis of Xenopus dsRNA adenosine deaminase cDNAs reveals similarities to DNA methyltransferases.
1997,
Pubmed
,
Xenbase
Jans,
Nuclear targeting signal recognition: a key control point in nuclear transport?
2000,
Pubmed
Jantsch,
Assembly and localization of the U1-specific snRNP C protein in the amphibian oocyte.
1992,
Pubmed
,
Xenbase
Kharrat,
Structure of the dsRNA binding domain of E. coli RNase III.
1995,
Pubmed
Kim,
Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing.
1994,
Pubmed
Krovat,
Comparative mutational analysis of the double-stranded RNA binding domains of Xenopus laevis RNA-binding protein A.
1996,
Pubmed
,
Xenbase
Kudo,
Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region.
1999,
Pubmed
LaCasse,
Nuclear localization signals overlap DNA- or RNA-binding domains in nucleic acid-binding proteins.
1995,
Pubmed
Lai,
Mutagenic analysis of double-stranded RNA adenosine deaminase, a candidate enzyme for RNA editing of glutamate-gated ion channel transcripts.
1995,
Pubmed
Lehmann,
The importance of internal loops within RNA substrates of ADAR1.
1999,
Pubmed
,
Xenbase
Liu,
Mechanism of interferon action: functionally distinct RNA-binding and catalytic domains in the interferon-inducible, double-stranded RNA-specific adenosine deaminase.
1996,
Pubmed
Liu,
Functionally distinct double-stranded RNA-binding domains associated with alternative splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase.
1997,
Pubmed
Liu,
Double-stranded RNA-specific adenosine deaminase: nucleic acid binding properties.
1998,
Pubmed
Melcher,
A mammalian RNA editing enzyme.
1996,
Pubmed
Michael,
The K nuclear shuttling domain: a novel signal for nuclear import and nuclear export in the hnRNP K protein.
1997,
Pubmed
,
Xenbase
Micklem,
Distinct roles of two conserved Staufen domains in oskar mRNA localization and translation.
2000,
Pubmed
Nakielny,
Transport of proteins and RNAs in and out of the nucleus.
1999,
Pubmed
Nakielny,
The hnRNP C proteins contain a nuclear retention sequence that can override nuclear export signals.
1996,
Pubmed
O'Connell,
Purification and properties of double-stranded RNA-specific adenosine deaminase from calf thymus.
1994,
Pubmed
,
Xenbase
O'Connell,
RNA editing: rewriting receptors.
1997,
Pubmed
O'Connell,
Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase.
1995,
Pubmed
Ohman,
In vitro analysis of the binding of ADAR2 to the pre-mRNA encoding the GluR-B R/G site.
2000,
Pubmed
Patterson,
Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase.
1995,
Pubmed
Peculis,
Localization of the nucleolar protein NO38 in amphibian oocytes.
1992,
Pubmed
,
Xenbase
Piñol-Roma,
Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm.
1992,
Pubmed
,
Xenbase
Polson,
Preferential selection of adenosines for modification by double-stranded RNA adenosine deaminase.
1994,
Pubmed
Ramos,
RNA recognition by a Staufen double-stranded RNA-binding domain.
2000,
Pubmed
Ryter,
Molecular basis of double-stranded RNA-protein interactions: structure of a dsRNA-binding domain complexed with dsRNA.
1998,
Pubmed
,
Xenbase
Saccomanno,
The cytoplasm of Xenopus oocytes contains a factor that protects double-stranded RNA from adenosine-to-inosine modification.
1994,
Pubmed
,
Xenbase
Siomi,
A nuclear localization domain in the hnRNP A1 protein.
1995,
Pubmed
Slavov,
Comparative analysis of the RED1 and RED2 A-to-I RNA editing genes from mammals, pufferfish and zebrafish.
2000,
Pubmed
Slavov,
Comparative analysis of the DRADA A-to-I RNA editing gene from mammals, pufferfish and zebrafish.
2000,
Pubmed
Steitz,
Immunoprecipitation of ribonucleoproteins using autoantibodies.
1989,
Pubmed
Verma,
Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation.
1995,
Pubmed
Wallace,
Protein incorporation by isolated amphibian oocytes. 3. Optimum incubation conditions.
1973,
Pubmed
,
Xenbase
Watanabe,
Involvement of CRM1, a nuclear export receptor, in mRNA export in mammalian cells and fission yeast.
1999,
Pubmed
