Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 11 to 20 of 27

Publication Record

Connections

Hyperphagia-mediated obesity in transgenic mice misexpressing the RNA-editing enzyme ADAR2.
Singh M, Kesterson RA, Jacobs MM, Joers JM, Gore JC, Emeson RB
(2007) J Biol Chem 282: 22448-59
MeSH Terms: Adenosine, Adenosine Deaminase, Animals, Caloric Restriction, Cytomegalovirus, Female, Inosine, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mutation, Obesity, Promoter Regions, Genetic, RNA-Binding Proteins, Rats
Show Abstract · Added August 13, 2010
ADAR2 is a double-stranded RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-specific conversion of adenosine to inosine. To examine the physiologic consequences resulting from ADAR2 misexpression, we have generated mutant mice expressing either wild-type or deaminase-deficient ADAR2 transgenes under the control of the human cytomegalovirus promoter. Transgenic mice expressing either wild-type or inactive ADAR2 isoforms demonstrated adult onset obesity characterized by hyperglycemia, hyperleptinemia, and increased adiposity. Paired feeding analysis revealed that mutant mice on caloric restriction had a growth rate and body composition indistinguishable from wild-type littermates, indicating that the observed obesity predominantly results from hyperphagia rather than a metabolic derangement. The observation that expression of catalytically inactive ADAR2 also is capable of producing an obese phenotype in mutant animals suggests that ADAR2 may possess additional biological activities beyond those required for the site-selective deamination of adenosine or may interfere with the actions of other double-stranded RNA-specific binding proteins in the cell.
2 Communities
2 Members
0 Resources
16 MeSH Terms
Substrate-dependent contribution of double-stranded RNA-binding motifs to ADAR2 function.
Xu M, Wells KS, Emeson RB
(2006) Mol Biol Cell 17: 3211-20
MeSH Terms: Adenosine Deaminase, Amino Acid Motifs, Animals, Cell Nucleus, Cells, Cultured, Conserved Sequence, Humans, Lysine, Mice, Phosphoproteins, Point Mutation, RNA Editing, RNA, Double-Stranded, RNA-Binding Proteins, Sequence Deletion
Show Abstract · Added January 17, 2014
ADAR2 is a double-stranded RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-specific conversion of adenosine to inosine (A-to-I). ADAR2 contains two tandem double-stranded RNA-binding motifs (dsRBMs) that are not only important for efficient editing of RNA substrates but also necessary for localizing ADAR2 to nucleoli. The sequence and structural similarity of these motifs have raised questions regarding the role(s) that each dsRBM plays in ADAR2 function. Here, we demonstrate that the dsRBMs of ADAR2 differ in both their ability to modulate subnuclear localization as well as to promote site-selective A-to-I conversion. Surprisingly, dsRBM1 contributes to editing activity in a substrate-dependent manner, indicating that dsRBMs recognize distinct structural determinants in each RNA substrate. Although dsRBM2 is essential for the editing of all substrates examined, a point mutation in this motif affects editing for only a subset of RNAs, suggesting that dsRBM2 uses unique sets of amino acid(s) for functional interactions with different RNA targets. The dsRBMs of ADAR2 are interchangeable for subnuclear targeting, yet such motif alterations do not support site-selective editing, indicating that the unique binding preferences of each dsRBM differentially contribute to their pleiotropic function.
1 Communities
2 Members
0 Resources
15 MeSH Terms
Structure and specific RNA binding of ADAR2 double-stranded RNA binding motifs.
Stefl R, Xu M, Skrisovska L, Emeson RB, Allain FH
(2006) Structure 14: 345-55
MeSH Terms: Adenosine Deaminase, Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Dimerization, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Magnetic Resonance, Biomolecular, Nucleic Acid Conformation, Protein Structure, Secondary, Protein Structure, Tertiary, RNA Editing, RNA, Double-Stranded, RNA-Binding Proteins, Rats, Sequence Alignment
Show Abstract · Added July 12, 2010
Adenosine deaminases that act on RNA (ADARs) site-selectively modify adenosines to inosines within RNA transcripts, thereby recoding genomic information. How ADARs select specific adenosine moieties for deamination is poorly understood. Here, we report NMR structures of the two double-stranded RNA binding motifs (dsRBMs) of rat ADAR2 and an NMR chemical shift perturbation study of the interaction of the two dsRBMs with a 71 nucleotide RNA encoding the R/G site of the GluR-B. We have identified the protein and the RNA surfaces involved in complex formation, allowing us to present an NMR-based model of the complex. We have found that dsRBM1 recognizes a conserved pentaloop, whereas dsRBM2 recognizes two bulged bases adjacent to the editing site, demonstrating RNA structure-dependent recognition by the ADAR2 dsRBMs. In vitro mutagenesis studies with both the protein and the RNA further support our structural findings.
1 Communities
1 Members
0 Resources
18 MeSH Terms
Altered RNA editing in mice lacking ADAR2 autoregulation.
Feng Y, Sansam CL, Singh M, Emeson RB
(2006) Mol Cell Biol 26: 480-8
MeSH Terms: Adenosine Deaminase, Alternative Splicing, Animals, Gene Expression, Male, Mice, Mice, Mutant Strains, Mutation, RNA Editing, RNA, Messenger, RNA-Binding Proteins
Show Abstract · Added August 13, 2010
ADAR2 is a double-stranded-RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-selective conversion of adenosine to inosine. Previous studies from our laboratory have demonstrated that ADAR2 can modify its own pre-mRNA to create a proximal 3' splice site containing a noncanonical adenosine-inosine dinucleotide. Alternative splicing to this proximal acceptor adds 47 nucleotides to the mature ADAR2 transcript, thereby resulting in the loss of functional ADAR2 protein expression due to premature translation termination in an alternate reading frame. To examine whether the editing of ADAR2 transcripts represents a negative autoregulatory strategy to modulate ADAR2 protein expression, we have generated genetically modified mice in which the ability of ADAR2 to edit its own pre-mRNA has been selectively ablated by deletion of a critical sequence (editing site complementary sequence [ECS]) required for adenosine-to-inosine conversion. Here we demonstrate that ADAR2 autoediting and subsequent alternative splicing are abolished in homozygous deltaECS mice and that ADAR2 protein expression is increased in numerous tissues compared to wild-type animals. The observed increases in ADAR2 protein expression correlate with the extent of ADAR2 autoediting observed with wild-type tissues and correspond to increases in the editing of ADAR2 substrates, indicating that ADAR2 autoediting is a key regulator of ADAR2 protein expression and activity in vivo.
2 Communities
1 Members
0 Resources
11 MeSH Terms
Resonance assignments of the double-stranded RNA-binding domains of adenosine deaminase acting on RNA 2 (ADAR2).
Stefl R, Skrisovska L, Xu M, Emeson RB, Allain FH
(2005) J Biomol NMR 31: 71-2
MeSH Terms: Adenosine Deaminase, Animals, Magnetic Resonance Spectroscopy, Protein Structure, Tertiary, RNA, Double-Stranded, RNA-Binding Proteins, Rats
Added July 12, 2010
1 Communities
1 Members
0 Resources
7 MeSH Terms
Structure and sequence determinants required for the RNA editing of ADAR2 substrates.
Dawson TR, Sansam CL, Emeson RB
(2004) J Biol Chem 279: 4941-51
MeSH Terms: Adenosine Deaminase, Alternative Splicing, Animals, Base Pairing, Base Sequence, Binding, Competitive, Cell Line, Exons, Humans, In Vitro Techniques, Introns, Kinetics, Models, Molecular, Molecular Sequence Data, Mutation, Nucleic Acid Conformation, RNA Editing, RNA Precursors, RNA-Binding Proteins, Rats, Recombinant Proteins, Substrate Specificity, Transfection
Show Abstract · Added July 12, 2010
ADAR2 is a double-stranded RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-specific conversion of adenosine to inosine. We have demonstrated previously that ADAR2 can modify its own pre-mRNA, leading to the creation of a proximal 3'-splice junction containing a non-canonical adenosine-inosine (A-I) dinucleotide. Alternative splicing to this proximal acceptor shifts the reading frame of the mature mRNA transcript, resulting in the loss of functional ADAR2 expression. Both evolutionary sequence conservation and mutational analysis support the existence of an extended RNA duplex within the ADAR2 pre-mRNA formed by base-pairing interactions between regions approximately 1.3-kilobases apart in intron 4 and exon 5. Characterization of ADAR2 pre-mRNA transcripts isolated from adult rat brain identified 16 editing sites within this duplex region, and sites preferentially modified by ADAR1 and ADAR2 have been defined using both tissue culture and in vitro editing systems. Statistical analysis of nucleotide sequences surrounding edited and non-edited adenosine residues have identified a nucleotide sequence bias correlating with ADAR2 site preference and editing efficiency. Among a mixed population of ADAR substrates, ADAR2 preferentially favors its own transcript, yet mutation of a poor substrate to conform to the defined nucleotide bias increases the ability of that substrate to be modified by ADAR2. These data suggest that both sequence and structural elements are required to define adenosine moieties targeted for specific ADAR2-mediated deamination.
1 Communities
1 Members
0 Resources
23 MeSH Terms
Modulation of RNA editing by functional nucleolar sequestration of ADAR2.
Sansam CL, Wells KS, Emeson RB
(2003) Proc Natl Acad Sci U S A 100: 14018-23
MeSH Terms: Adenosine Deaminase, Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cell Nucleolus, In Vitro Techniques, Mice, Molecular Sequence Data, NIH 3T3 Cells, RNA Editing, RNA Precursors, RNA, Double-Stranded, RNA, Ribosomal, RNA-Binding Proteins, Rats, Recombinant Fusion Proteins, Substrate Specificity
Show Abstract · Added January 17, 2014
The adenosine deaminases that act on RNA (ADARs) catalyze the site-specific conversion of adenosine to inosine (A to I) in primary mRNA transcripts, thereby affecting the splicing pattern or coding potential of mature mRNAs. Although the subnuclear localization of A-to-I editing has not been precisely defined, ADARs have been shown to act before splicing, suggesting that they function near nucleoplasmic sites of transcription. Here we demonstrate that ADAR2, a member of the vertebrate ADAR family, is concentrated in the nucleolus, a subnuclear domain disparate from the sites of mRNA transcription. Selective inhibition of ribosomal RNA synthesis or the introduction of mutations in the double-stranded RNA-binding domains within ADAR2 results in translocation of the protein to the nucleoplasm, suggesting that nucleolar association of ADAR2 depends on its ability to bind to ribosomal RNA. Fluorescence recovery after photobleaching reveals that ADAR2 can shuttle rapidly between subnuclear compartments. Enhanced translocation of endogenous ADAR2 from the nucleolus to the nucleoplasm results in increased editing of endogenous ADAR2 substrates. These observations indicate that the nucleolar localization of ADAR2 represents an important mechanism by which RNA editing can be modulated by the sequestration of enzymatic activity from potential RNA substrates in the nucleoplasm.
1 Communities
2 Members
0 Resources
18 MeSH Terms
Serotonin-2C receptor pre-mRNA editing in rat brain and in vitro by splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase ADAR1.
Liu Y, Emeson RB, Samuel CE
(1999) J Biol Chem 274: 18351-8
MeSH Terms: Adenosine Deaminase, Animals, Brain, COS Cells, DNA-Binding Proteins, Enzyme Induction, Interferons, RNA Editing, RNA Precursors, RNA Splicing, RNA, Double-Stranded, RNA-Binding Proteins, Rats, Receptor, Serotonin, 5-HT2C, Receptors, Serotonin, Transcription, Genetic
Show Abstract · Added July 12, 2010
The interferon-inducible RNA-specific adenosine deaminase (ADAR1) is an RNA editing enzyme implicated in the site-selective deamination of adenosine to inosine in cellular pre-mRNAs. The pre-mRNA for the rat serotonin-2C receptor (5-HT2CR) possesses four editing sites (A, B, C, and D), which undergo A-to-I nucleotide conversions that alter the signaling function of the encoded G-protein-coupled receptor. Measurements of 5-HT2CR pre-mRNA editing in vitro revealed site-specific deamination catalyzed by ADAR1. Three splice site variants, ADAR1-a, -b, and -c, all efficiently edited the A site of 5-HT2CR pre-mRNA, but the D site did not serve as an efficient substrate for any of the ADAR1 variants. Mutational analysis of the three double-stranded (ds) RNA binding motifs present in ADAR1 revealed a different relative importance of the individual dsRNA binding motifs for deamination of the A site of 5-HT2CR and synthetic dsRNA substrates. Quantitative reverse transcription-polymerase chain reaction analyses demonstrated that the 5-HT2CR pre-mRNA was most highly expressed in the choroid plexus of rat brain. However, ADAR1 and the related deaminase ADAR2 showed significant expression in all regions of the brain examined, including cortex, hippocampus, olfactory bulb, and striatum, where the 5-HT2CR pre-mRNA was extensively edited.
1 Communities
1 Members
0 Resources
16 MeSH Terms
Regulation of alternative splicing by RNA editing.
Rueter SM, Dawson TR, Emeson RB
(1999) Nature 399: 75-80
MeSH Terms: Adenosine, Adenosine Deaminase, Alternative Splicing, Animals, Base Sequence, Cell Line, DNA, Gene Expression Regulation, Enzymologic, Guanosine, Humans, Molecular Sequence Data, Mutagenesis, Site-Directed, RNA Editing, RNA, Messenger, RNA-Binding Proteins, Rats, Transfection, Tumor Cells, Cultured
Show Abstract · Added July 12, 2010
The enzyme ADAR2 is a double-stranded RNA-specific adenosine deaminase which is involved in the editing of mammalian messenger RNAs by the site-specific conversion of adenosine to inosine. Here we identify several rat ADAR2 mRNAs produced as a result of two distinct alternative splicing events. One such splicing event uses a proximal 3' acceptor site, adding 47 nucleotides to the ADAR2 coding region, changing the predicted reading frame of the mature ADAR2 transcript. Nucleotide-sequence analysis of ADAR2 genomic DNA revealed the presence of adenosine-adenosine (AA) and adenosine-guanosine (AG) dinucleotides at these proximal and distal alternative 3' acceptor sites, respectively. Use of the proximal 3' acceptor depends upon the ability of ADAR2 to edit its own pre-mRNA, converting the intronic AA to an adenosine-inosine (AI) dinucleotide which effectively mimics the highly conserved AG sequence normally found at 3' splice junctions. Our observations indicate that RNA editing can serve as a mechanism for regulating alternative splicing and they suggest a novel strategy by which ADAR2 can modulate its own expression.
1 Communities
1 Members
0 Resources
18 MeSH Terms
A standardized nomenclature for adenosine deaminases that act on RNA.
Bass BL, Nishikura K, Keller W, Seeburg PH, Emeson RB, O'Connell MA, Samuel CE, Herbert A
(1997) RNA 3: 947-9
MeSH Terms: Adenosine Deaminase, RNA, RNA Splicing, Terminology as Topic
Added July 12, 2010
1 Communities
1 Members
0 Resources
4 MeSH Terms