Adar

Summary

Gene Symbol: Adar
Description: Adenosine deaminase acting on RNA
Alias: ADAR, ADAR1, CG12598, Dmel\CG12598, EG:BACN35H14.1, adar, adr, cg12598, dADAR, dAdar, dadar, hypnos-2, adenosine deaminase acting on RNA, Adar-PA, Adar-PB, Adar-PC, Adar-PD, Adar-PE, Adar-PF, Adar-PH, Adar-PI, Adar-PJ, Adar-PK, Adar-PM, Adar-PN, Adar-PO, Adar-PP, CG12598-PA, CG12598-PB, CG12598-PC, CG12598-PD, CG12598-PE, CG12598-PF, CG12598-PH, CG12598-PI, CG12598-PJ, CG12598-PK, CG12598-PM, CG12598-PN, CG12598-PO, CG12598-PP, adenosine deaminases acting on RNA, hypnos-2, hypoxia, anoxia, sensitive 2
Species: fruit fly

Top Publications

  1. Palladino M, Keegan L, O Connell M, Reenan R. A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell. 2000;102:437-49 pubmed
    ..Drosophila possesses a candidate editing enzyme, dADAR. Here, we describe dADAR deletion mutants that lack ADAR activity in extracts...
  2. Xia S, Yang J, Su Y, Qian J, Ma E, Haddad G. Identification of new targets of Drosophila pre-mRNA adenosine deaminase. Physiol Genomics. 2005;20:195-202 pubmed
    b>Adenosine deaminase acting on RNA (ADAR) in Drosophila and mammals has recently become the target of numerous investigations. It is now clear that this protein has a number of functions in the nervous system...
  3. Gallo A, Keegan L, Ring G, O Connell M. An ADAR that edits transcripts encoding ion channel subunits functions as a dimer. EMBO J. 2003;22:3421-30 pubmed
    In this report, we establish that Drosophila ADAR (adenosine deaminase acting on RNA) forms a dimer on double-stranded (ds) RNA, a process essential for editing activity...
  4. Bhalla T, Rosenthal J, Holmgren M, Reenan R. Control of human potassium channel inactivation by editing of a small mRNA hairpin. Nat Struct Mol Biol. 2004;11:950-6 pubmed
    ..1 mRNA sequence directs efficient modification of one adenosine by human adenosine deaminase acting on RNA 2 (hADAR2). Mutational analysis shows that this region adopts a hairpin structure...
  5. Ingleby L, Maloney R, Jepson J, Horn R, Reenan R. Regulated RNA editing and functional epistasis in Shaker potassium channels. J Gen Physiol. 2009;133:17-27 pubmed publisher
    ..Our results unmask allosteric communication across disparate regions of the channel protein and between evolved and regulated amino acid changes introduced by RNA editing. ..
  6. St Laurent G, Tackett M, Nechkin S, Shtokalo D, Antonets D, Savva Y, et al. Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in Drosophila. Nat Struct Mol Biol. 2013;20:1333-9 pubmed publisher
    ..Finally, editing regulates expression levels of target mRNAs and strongly correlates with alternative splicing. ..
  7. Maldonado C, Alicea D, Gonzalez M, Bykhovskaia M, Marie B. Adar is essential for optimal presynaptic function. Mol Cell Neurosci. 2013;52:173-80 pubmed publisher
    ..Across phyla, loss of the enzyme responsible for RNA editing, Adar, leads to behavioral changes, impaired locomotion, neurodegeneration and death...
  8. Ma E, Gu X, Wu X, Xu T, Haddad G. Mutation in pre-mRNA adenosine deaminase markedly attenuates neuronal tolerance to O2 deprivation in Drosophila melanogaster. J Clin Invest. 2001;107:685-93 pubmed
    ..This gene encodes a Drosophila pre-mRNA adenosine deaminase (dADAR) and is expressed almost exclusively in the adult central nervous system...
  9. Keegan L, Brindle J, Gallo A, Leroy A, Reenan R, O Connell M. Tuning of RNA editing by ADAR is required in Drosophila. EMBO J. 2005;24:2183-93 pubmed
    ..Adar (adenosine deaminase acting on RNA) mutant flies expressing only genome-encoded, unedited isoforms of ion-channel subunits are viable ..

More Information

Publications47

  1. Jepson J, Reenan R. Adenosine-to-inosine genetic recoding is required in the adult stage nervous system for coordinated behavior in Drosophila. J Biol Chem. 2009;284:31391-400 pubmed publisher
    b>Adenosine deaminases acting on RNA (ADARs) catalyze the deamination of adenosine to inosine in double-stranded RNA templates, a process known as RNA editing...
  2. Keegan L, McGurk L, Palavicini J, Brindle J, Paro S, Li X, et al. Functional conservation in human and Drosophila of Metazoan ADAR2 involved in RNA editing: loss of ADAR1 in insects. Nucleic Acids Res. 2011;39:7249-62 pubmed publisher
    ..Vertebrates have two ADAR-editing enzymes that are catalytically active; ADAR1 and ADAR2. We show that human ADAR2 rescues Drosophila Adar mutant phenotypes...
  3. Li X, Overton I, Baines R, Keegan L, O Connell M. The ADAR RNA editing enzyme controls neuronal excitability in Drosophila melanogaster. Nucleic Acids Res. 2014;42:1139-51 pubmed publisher
    ..On the other hand, overexpressing an adult dADAR isoform with high enzymatic activity ubiquitously during larval and pupal stages is lethal...
  4. Jepson J, Savva Y, Yokose C, Sugden A, Sahin A, Reenan R. Engineered alterations in RNA editing modulate complex behavior in Drosophila: regulatory diversity of adenosine deaminase acting on RNA (ADAR) targets. J Biol Chem. 2011;286:8325-37 pubmed publisher
    ..are re-coded at the RNA level via the deamination of particular adenosines to inosine by adenosine deaminases acting on RNA (ADARs)...
  5. Palladino M, Keegan L, O Connell M, Reenan R. dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly developmentally regulated and is itself a target for RNA editing. RNA. 2000;6:1004-18 pubmed
    ..identified a homolog of the ADAR (adenosine deaminases that act on RNA) class of RNA editases from Drosophila, dADAR. The dADAR locus has been localized to the 2B6-7 region of the X chromosome and the complete genomic sequence ..
  6. Bhogal B, Jepson J, Savva Y, Pepper A, Reenan R, Jongens T. Modulation of dADAR-dependent RNA editing by the Drosophila fragile X mental retardation protein. Nat Neurosci. 2011;14:1517-24 pubmed publisher
    ..the Drosophila fragile X homolog (dFMR1) biochemically interacted with the adenosine-to-inosine RNA-editing enzyme dADAR. Adar and Fmr1 mutant larvae exhibited distinct morphological neuromuscular junction (NMJ) defects...
  7. Heale B, Keegan L, McGurk L, Michlewski G, Brindle J, Stanton C, et al. Editing independent effects of ADARs on the miRNA/siRNA pathways. EMBO J. 2009;28:3145-56 pubmed publisher
    b>Adenosine deaminases acting on RNA (ADARs) are best known for altering the coding sequences of mRNA through RNA editing, as in the GluR-B Q/R site...
  8. Savva Y, Jepson J, Sahin A, Sugden A, Dorsky J, Alpert L, et al. Auto-regulatory RNA editing fine-tunes mRNA re-coding and complex behaviour in Drosophila. Nat Commun. 2012;3:790 pubmed publisher
    ..many messenger RNAs involved in neuro-transmission are re-coded at the RNA level by the RNA-editing enzyme, dADAR, leading to the incorporation of amino acids that are not directly encoded by the genome...
  9. Hoopengardner B, Bhalla T, Staber C, Reenan R. Nervous system targets of RNA editing identified by comparative genomics. Science. 2003;301:832-6 pubmed
    ..RNAs undergo genetic recoding by modification of adenosine to inosine, a reaction catalyzed by the adenosine deaminases acting on RNA (ADARs). Discovery of these edited transcripts has always been serendipitous...
  10. Savva Y, Jepson J, Chang Y, Whitaker R, Jones B, St Laurent G, et al. RNA editing regulates transposon-mediated heterochromatic gene silencing. Nat Commun. 2013;4:2745 pubmed publisher
    ..Furthermore, we show that the trigger RNA is edited and that dADAR serves as a key regulator of chromatin state...
  11. Chen L, Rio D, Haddad G, Ma E. Regulatory role of dADAR in ROS metabolism in Drosophila CNS. Brain Res Mol Brain Res. 2004;131:93-100 pubmed
    ..Mutations of Drosophila ADAR (dADAR) results in neuronal dysfunction and hypersensitivity to oxygen deprivation...
  12. Haddad G, Sun Y, Wyman R, Xu T. Genetic basis of tolerance to O2 deprivation in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1997;94:10809-12 pubmed
    ..These studies show that anoxic tolerance can be genetically dissected. ..
  13. Driscoll M, Gerstbrein B. Dying for a cause: invertebrate genetics takes on human neurodegeneration. Nat Rev Genet. 2003;4:181-94 pubmed
    ..An emerging theme is that neuronal crises of distinct origins might converge to disrupt common cellular functions, such as protein folding and turnover. ..
  14. Lakshmi G, Ghosh S, Jones G, Parikh R, Rawlins B, Vaughn J. An RNA electrophoretic mobility shift and mutational analysis of rnp-4f 5'-UTR intron splicing regulatory proteins in Drosophila reveals a novel new role for a dADAR protein isoform. Gene. 2012;511:161-8 pubmed publisher
    ..probe with embryo protein extract is shown to result in two shifted RNA-protein bands, and protein extract from a dADAR null mutant fly line results in only one shifted band...
  15. Rieder L, Staber C, Hoopengardner B, Reenan R. Tertiary structural elements determine the extent and specificity of messenger RNA editing. Nat Commun. 2013;4:2232 pubmed publisher
    The specificity and extent of RNA editing by ADAR enzymes is determined largely by local primary sequence and secondary structural imperfections in duplex RNA...
  16. Reenan R. The RNA world meets behavior: A-->I pre-mRNA editing in animals. Trends Genet. 2001;17:53-6 pubmed
    ..Pre-mRNA editing by adenosine deaminases acting on RNA (ADARs) provides an additional mechanism for introducing protein diversity and has primarily been ..
  17. Keegan L, Gallo A, O Connell M. Development. Survival is impossible without an editor. Science. 2000;290:1707-9 pubmed
    ..In a Perspective, Keegan, Gallo and O'Connell explore new results showing that activity of the editing enzyme ADAR1 is crucial for normal development of red blood cells in mouse embryos.
  18. Ramaswami G, Zhang R, Piskol R, Keegan L, Deng P, O Connell M, et al. Identifying RNA editing sites using RNA sequencing data alone. Nat Methods. 2013;10:128-32 pubmed publisher
    ..We also found that human genes harboring conserved editing sites within Alu repeats are enriched for neuronal functions. ..
  19. Grauso M, Reenan R, Culetto E, Sattelle D. Novel putative nicotinic acetylcholine receptor subunit genes, Dalpha5, Dalpha6 and Dalpha7, in Drosophila melanogaster identify a new and highly conserved target of adenosine deaminase acting on RNA-mediated A-to-I pre-mRNA editing. Genetics. 2002;160:1519-33 pubmed
    ..The Dalpha6 transcript is a target of the Drosophila adenosine deaminase acting on RNA (dADAR). This is the first case for any organism where a nAChR gene is the target of mRNA editing...
  20. Barraud P, Heale B, O Connell M, Allain F. Solution structure of the N-terminal dsRBD of Drosophila ADAR and interaction studies with RNA. Biochimie. 2012;94:1499-509 pubmed publisher
    ..vertebrates have two catalytically active enzymes, namely ADAR1 and ADAR2, Drosophila has a single ADAR protein (dADAR) related to ADAR2...
  21. Jepson J, Savva Y, Jay K, Reenan R. Visualizing adenosine-to-inosine RNA editing in the Drosophila nervous system. Nat Methods. 2011;9:189-94 pubmed publisher
    ..a fluorescent reporter sensitive to Drosophila melanogaster adenosine deaminase that acts on RNA (dADAR) activity and alterations in dADAR autoregulation...
  22. Chen J, Lakshmi G, Hays D, McDowell K, Ma E, Vaughn J. Spatial and temporal expression of dADAR mRNA and protein isoforms during embryogenesis in Drosophila melanogaster. Differentiation. 2009;78:312-20 pubmed publisher
    b>Adenosine Deaminases Acting on RNA (ADARs) function to co-transcriptionally deaminate specific (or non-specific) adenosines to inosines within pre-mRNAs, using double-stranded RNAs as substrate...
  23. Wang Z, Lin H. The division of Drosophila germline stem cells and their precursors requires a specific cyclin. Curr Biol. 2005;15:328-33 pubmed
    ..Our results indicate that stem cells may use specific cell cycle regulators for their division. ..
  24. Chen J, Concel V, Bhatla S, Rajeshwaran R, Smith D, Varadarajan M, et al. Alternative splicing of an rnp-4f mRNA isoform retaining an evolutionarily-conserved 5'-UTR intronic element is developmentally regulated and shown via RNAi to be essential for normal central nervous system development in Drosophila melanogaster. Gene. 2007;399:91-104 pubmed
    ..Long rnp-4f mRNA knockdown via RNAi reveals a variety of CNS abnormalities, which leads us to postulate that this isoform acts upstream of other genes which have been shown to be important for normal CNS development. ..
  25. Sapiro A, Deng P, Zhang R, Li J. Cis regulatory effects on A-to-I RNA editing in related Drosophila species. Cell Rep. 2015;11:697-703 pubmed publisher
    Adenosine-to-inosine RNA editing modifies maturing mRNAs through the binding of adenosine deaminase acting on RNA (Adar) proteins to double-stranded RNA structures in a process critical for neuronal function...
  26. McGurk L, Morrison H, Keegan L, Sharpe J, O Connell M. Three-dimensional imaging of Drosophila melanogaster. PLoS ONE. 2007;2:e834 pubmed
    ..vacuoles from within the head capsule of flies that suffer from age-related neurodegeneration due to a lack of ADAR mediated RNA-editing. In addition we have visualized tau-lacZ expression in 2D and 3D...
  27. Rodriguez J, Menet J, Rosbash M. Nascent-seq indicates widespread cotranscriptional RNA editing in Drosophila. Mol Cell. 2012;47:27-37 pubmed publisher
    The RNA editing enzyme ADAR chemically modifies adenosine (A) to inosine (I), which is interpreted by the ribosome as a guanosine...
  28. Ghosh S, Wang Y, Cook J, Chhiba L, Vaughn J. A molecular, phylogenetic and functional study of the dADAR mRNA truncated isoform during Drosophila embryonic development reveals an editing-independent function. Open J Anim Sci. 2013;3:20-30 pubmed
    b>Adenosine Deaminases Acting on RNA (ADARs) have been studied in many animal phyla, where they have been shown to deaminate specific adenosines into inosines in duplex mRNA regions...
  29. Robinson J, Paluch J, Dickman D, Joiner W. ADAR-mediated RNA editing suppresses sleep by acting as a brake on glutamatergic synaptic plasticity. Nat Commun. 2016;7:10512 pubmed publisher
    ..Here we demonstrate that deficiencies in the RNA-editing gene Adar increase sleep due to synaptic dysfunction in glutamatergic neurons in Drosophila...
  30. Buchumenski I, Bartok O, Ashwal Fluss R, Pandey V, Porath H, Levanon E, et al. Dynamic hyper-editing underlies temperature adaptation in Drosophila. PLoS Genet. 2017;13:e1006931 pubmed publisher
    In Drosophila, A-to-I editing is prevalent in the brain, and mutations in the editing enzyme ADAR correlate with specific behavioral defects. Here we demonstrate a role for ADAR in behavioral temperature adaptation in Drosophila...
  31. McBride S, Choi C, Schoenfeld B, Bell A, Liebelt D, Ferreiro D, et al. Pharmacological and genetic reversal of age-dependent cognitive deficits attributable to decreased presenilin function. J Neurosci. 2010;30:9510-22 pubmed publisher
    ..They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced. ..
  32. Hughes M, Grant G, Paquin C, Qian J, Nitabach M. Deep sequencing the circadian and diurnal transcriptome of Drosophila brain. Genome Res. 2012;22:1266-81 pubmed publisher
    ..These studies demonstrate extensive circadian control of ncRNA expression, reveal the extent of clock control of alternative splicing and RNA editing, and provide a novel, genome-wide map of splicing in Drosophila brain. ..
  33. Marcucci R, Romano M, Feiguin F, O Connell M, Baralle F. Dissecting the splicing mechanism of the Drosophila editing enzyme; dADAR. Nucleic Acids Res. 2009;37:1663-71 pubmed publisher
    In Drosophila melanogaster, the expression of adenosine deaminase acting on RNA is regulated by transcription and alternative splicing so that at least four different isoforms are generated that have a tissue-specific splicing pattern...
  34. Chawla G, Sokol N. ADAR mediates differential expression of polycistronic microRNAs. Nucleic Acids Res. 2014;42:5245-55 pubmed publisher
    ..Here we show that RNA editing by Drosophila ADAR modulates the expression of three co-transcribed miRNAs encoded by the evolutionarily conserved let-7-Complex (let-..
  35. Stapleton M, Carlson J, Brokstein P, Yu C, Champe M, George R, et al. A Drosophila full-length cDNA resource. Genome Biol. 2002;3:RESEARCH0080 pubmed
    ..Clones were eliminated either because they carry single nucleotide discrepancies, which most probably result from reverse transcriptase errors, or because they are truncated and contain only part of the protein-coding sequence. ..
  36. Rieder L, Savva Y, Reyna M, Chang Y, Dorsky J, Rezaei A, et al. Dynamic response of RNA editing to temperature in Drosophila. BMC Biol. 2015;13:1 pubmed publisher
    ..In addition, we show that expression of the editing enzyme, ADAR (adenosine deaminase acting on RNA), is dramatically decreased at elevated temperatures, partially, but not fully, explaining some ..
  37. Stocker J, Huang H, Wang H, Chang H, Chiu C, Cho C, et al. Reduction of RNA A-to-I editing in Drosophila acclimated to heat shock. Kaohsiung J Med Sci. 2013;29:478-83 pubmed publisher
    ..This supports the hypothesis that cells and organisms respond to stressful environments by ADAR (adenosine deaminase acting on RNA)-mediated RNA editing...
  38. Diegelmann S, Nieratschker V, Werner U, Hoppe J, Zars T, Buchner E. The conserved protein kinase-A target motif in synapsin of Drosophila is effectively modified by pre-mRNA editing. BMC Neurosci. 2006;7:76 pubmed
    ..the synapsin pre-mRNA can form a double-stranded RNA structure that is required for editing by the adenosine deaminase acting on RNA (ADAR) enzyme...