1887

Chapter 19 : Adenosine-to-Inosine Conversion in mRNA

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in
Zoomout

Adenosine-to-Inosine Conversion in mRNA, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555818296/9781555811334_Chap19-1.gif /docserver/preview/fulltext/10.1128/9781555818296/9781555811334_Chap19-2.gif

Abstract:

The conversion of adenosine to inosine (A-to-I) by RNA editing, at specific positions within RNAs, represents an increasingly common posttranscriptional modification for generating diversity and flexibility in eukaryotic gene expression. This chapter describes a number of mRNA substrates that undergo A-to-I editing events, the effects that such alterations in coding potential have upon protein function, and the candidate enzymes responsible for such posttranscriptional modifications. While nucleotide sequence analyses have revealed the presence of a CGG codon encoding the critical regulatory arginine residue within the TM2 region of GluR-B cDNAs, a glutamine (CAG) codon was found in GluR-B genomic DNA at this position Q/R site. The editing of RNAs encoding glutamate receptor subunits results from the conversion of genomically encoded adenosine residues to the guanosine-like nucleotides found in cDNAs generated from mature GluR mRNA transcripts. The hepatitis delta virus (HDV) is a subviral human pathogen whose packaging and propagation are dependent on concurrent infection with the hepatitis B virus. Recent studies of RNA editing in polyomavirus have suggested that this posttranscriptional modification represents a mechanism by which RNA transcripts expressed early after viral infection are inactivated subsequent to viral DNA replication (the late phase). While future work will further define the cellular and molecular basis for dsRNA adenosine deamination, the functional consequences of subtle A-to-I changes in mRNAs and the alterations in amino acid sequence for resultant proteins are bound to be profound.

Citation: Rueter S, Emeson R. 1998. Adenosine-to-Inosine Conversion in mRNA, p 343-361. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch19

Key Concept Ranking

Avian leukosis virus
0.47146484
Hepatitis delta virus
0.46433362
Hepatitis B virus
0.44124073
Plasma Membrane
0.439137
0.47146484
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of Figure 1
Figure 1

A-to-I editing events in transcripts encoding non-NMDA glutamatc receptor subunits. A schematic representation of the predicted topology for GluR-A is presented indicating the relative positions of amino acid alterations produced as a result of A-to-I editing events and the location of the flip/flop domain (black rectangle); the topology of subunits other than GluR-A ( ) has not been determined. The posttranscriptional conversion of adenosine to inosine can be seen as an A-to-G discrepancy between the nucleotide sequences of genomic and complementary DNA (cDNA). The genomic (upper), cDNA (lower) and predicted amino acid alterations resulting from these editing events are presented.

Citation: Rueter S, Emeson R. 1998. Adenosine-to-Inosine Conversion in mRNA, p 343-361. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch19
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Predicted secondary structure of pre-mRNA transcripts encoding non-NMDA receptor subunits (GluR-B, GluR-5, and GluR-6), the 2C subtype of serotonin receptor (5-HTR) and the hepatitis delta virus (HDV) antigenome in the regions of major editing modifications using an RNA folding algorithm (RNAFOLD; Scientific & Educational Software). The positions of edited nucleotides are indicated by open circles, intron-exon boundaries are designated, and nucleotides omitted from the figure are indicated in the loops. Nucleotide coordinates are relative to the Q/R, R/G or A editing sites.

Citation: Rueter S, Emeson R. 1998. Adenosine-to-Inosine Conversion in mRNA, p 343-361. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch19
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Experimental strategy for determining the identity of a modified nucleotide(s) subsequent to RNA editing. A biochemical strategy is presented in which an RNA substrate uniformly labeled with [-P]-ATP is subjected to in vitro editing using HeLa cell nuclear extract as a source of enzymatic activity. The resulting in vitro reaction product is digested to completion with nuclease P1, yielding nucleotide 5′-monophosphates that can be resolved by thin-layer chromatography.

Citation: Rueter S, Emeson R. 1998. Adenosine-to-Inosine Conversion in mRNA, p 343-361. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch19
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

RNA editing of 5-HTR transcripts. (A) Nucleotide and predicted amino acid sequence alignments between 5-HTR genomic and cDNA sequences; A-to-G nucleotide discrepancies and predicted alterations in amino acid sequence are indicated in inverse and underlined lettering, respectively. (B) A schematic representation of the predicted topology for the 5-HT receptor is presented, indicating the sites of amino acid alteration within the second intracellular loop resulting from RNA editing events. The amino acid sequence of the 5-HTR is indicated with the one-letter amino acid code ( ).

Citation: Rueter S, Emeson R. 1998. Adenosine-to-Inosine Conversion in mRNA, p 343-361. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch19
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Alternatively spliced variants of human ADAR1 and ADAR2 mRNA produce multiple protein isoforms. Schematic representations of ADAR1 (A) and ADAR2 (B) protein isoforms are presented, indicating the locations of the putative nuclear localization signal (NLS; vertical stripe), Z-DNA binding domain (Z; black), dsRNA-binding domains (gray) and the adenosine deaminase domain (angled stripe). The location of zinc-coordination residues within the deaminase domain are designated by asterisks and the amino acid coordinates for each domain, relative to the amino terminus, are indicated. The specific amino acid residues deleted in the ADAR1b and ADAR1c isoforms or inserted in the deaminase domain of the ADAR2b and ADAR2c isoforms (Crosshatch) are indicated, as well as the amino acid residues present in unique ADAR2 carboxyl termini (black) with the one-letter amino acid code.

Citation: Rueter S, Emeson R. 1998. Adenosine-to-Inosine Conversion in mRNA, p 343-361. In Grosjean H, Benne R (ed), Modification and Editing of RNA. ASM Press, Washington, DC. doi: 10.1128/9781555818296.ch19
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555818296.chap19
1. Bass, B. L.,, H. Weintraub,, R. Cattaneo,, and M. A. Billeter. 1989. Biased hypermutation of viral RNA genomes could be due to unwinding/modification of double-stranded RNA. Cell 56: 331.
2. Bass, B. L.,, and H. Weintraub. 1987. A developmentally regulated activity that unwinds RNA duplexes. Cell 48: 607 613.
3. Bass, B. L.,, and H. Weintraub. 1988. An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell 55: 1089 1098.
4. Bass, B. L., 1993. RNA editing, p. 383 418. In R. Gesteland, and J. Atkins (ed.), The RNA World. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
5. Bass, B. L. 1997. RNA editing and hypermutation by adenosine deamination. Trends Biochem. Set. 22: 157 162.
6. Bass, B. L.,, K., Nishikura,, W. Keller,, P. H. Seeburg,, R. B. Emeson,, M. A. O'Connell,, C. E. Samuel,, and A. Herbert. 1997. A standardized nomenclature for adenosine deaminases that act on RNA. RNA 3: 947 949.
7. Betts, L.,, S. Xiang,, S. A. Short,, R. Wolfenden,, and C. W. Carter, Jr. 1994. Cytidine deaminase. The 2.3 Å crystal structure of an enzyme: transition-state analog complex. J. Mol. Biol. 235: 635 656.
8. Bezanilla, F.,, and E. Stefani. 1994. Voltage-dependent gating of ionic channels. Annu. Rev. Biophys. Biomol. Struct. 23: 819 846.
9. Billeter, M. A.,, and R. Cattaneo,. 1991. Molecular biology of defective measles virus in the human central nervous system, p. 323 345. In D. W. Kingsbury (ed.), The Paramyxoviruses. Plenum Press, New York, N.Y.
10. Billeter, M. A.,, R. Cattaneo,, P. Spielhofer,, K. Kaelin,, M. Huber,, A. Schmid,, K. Baczko,, and V. ter Meulen. 1994. Generation and properties of measles virus mutations typically associated with subacute sclerosing panencephalitis. Ann. N. Y. Acad. Sci. 724: 367 377.
11. Birnbaumer, L. 1992. Receptor-to-effector signaling through G proteins: roles for beta gamma dimers as well as alpha subunits. Cell 71: 1069 1072.
12. Björk, G. R., 1995. Biosynthesis and function of modified nucleosides, p. 165 205. In D. Söll, and U. L. RajBhandary (ed.), tRNA: Structure, Biosynthesis, and Function. American Society for Microbiology, Washington, D.C.
13. Bliss, T. V. P.,, and G. L. Collingridge. 1993. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361: 31 39.
14. Bonino, F.,, K. H. Heermann,, M. Rizzetto,, and W. H. Gerlich. 1986. Hepatitis delta virus: protein composition of delta antigen and its hepatitis B virus-derived envelope. J. Virol. 58: 945 950.
15. Boulter, J.,, M. Hollmann,, A. O'Shea-Greenfield,, M. Hartley,, E. Deneris,, C. Maron,, and S. Heinemann. 1989. Molecular cloning and functional xpression of glutamate receptor subunit genes. Science 249: 1033 1037.
16. Burd, C. G.,, and G. Dreyfuss. 1994. Conserved structures and diversity of functions of RNA-binding proteins. Science 265: 615 621.
17. Burnashev, N.,, A. Khodorova,, P. Jonas,, P. J. Helm,, W. Wisden,, H. Monyer,, P. H. Seeburg,, and B. Sakmann. 1992a. Calcium-permeable AMPA-kainate receptors in fusiform cerebellar glial cells. Science 256: 1566 1570.
18. Burnashev, N.,, H. Monyer,, P. H. Seeburg,, and B. Sakmann. 1992b. Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron 8: 89 98.
19. Burns, C. M.,, H. Chu,, S. M. Rueter,, L. K. Hutchinson,, H. Canton,, E. Sanders-Bush,, and R. B. Emeson. 1997. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387: 303 308.
20. Casey, J. L.,, K. F. Bergmann,, T. L. Brown,, and J. L. Gerin. 1992. Structural requirements for RNA editing in hepatitis δ virus: evidence for a uridine-to-cytidine editing mechanism. Proc. Natl. Acad. Sci. USA 89: 7149 7153.
21. Casey, J. L.,, and J. L. Gerin. 1995. Hepatitis D virus RNA editing: specific modification of adenosine in the antigenomic RNA. J. Virol. 69: 7593 7600.
22. Cattaneo, R.,, A. Schmid,, D. Eschle,, K. Baczko,, V. ter Meulen,, and M. A. Billeter. 1988. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell 55: 255 265.
23. Cattaneo, R. 1994. Biased (A→I) hypermutation of animal RNA virus genomes. Curr. Opin. Genet. Dev. 4: 895 900.
24. Chao, M.,, S.-Y. Hsieh,, and J. Taylor. 1990. Role of two forms of hepatitis delta virus antigen: evidence for a mechanism of self-limited genome replication. J. Virol. 64: 5066 5069.
25. Chen, P.-J.,, G. Kalpana,, J. Goldberg,, W. Mason,, B. Werner,, J. Gerin,, and J. Taylor. 1986. The structure and replication of the genome of the hepatitis delta virus. Proc. Natl. Acad. Sci. USA 83: 8774 8778.
26. Choi, D. W.,, and S. M. Rothman. 1990. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu. Rev. Neurosci. 13: 171 182.
27. Collingridge, G. L.,, and W. Singer. 1990. Excitatory amino acid receptors and synaptic plasticity. Trends Pharmacol. Sci. 11: 290 296.
28. Davidson, N. O. 1993. Apolipoprotein B mRNA editing: a key controlling element targeting fats to proper tissue. Ann. Med. 25: 539 543.
29. Dingledine, R.,, R. I. Hume,, and S. F. Heinemann. 1992. Structural determinants of barium permeation and rectification in non-NMDA glutamate receptor channels. J. Neurosci. 12: 4080 4087.
30. Dubinsky, J. M.,, and S. M. Rothman. 1991. Intracellular calcium concentrations during "chemical hypoxia" and excitotoxic neuronal injury. J. Neurosci. 11: 2545 2551.
31. Dubovsky, S. L,, and M. Thomas. 1995. Serotonergic mechanisms and current and future psychiatric practice. J. Clin. Psychiatry 2: 38 48.
32. Egebjerg, J.,, and S. F. Heinemann. 1993. Ca 2+ permeability of unedited and edited versions of the kainate selective glutamate receptor GluR6. Proc. Natl. Acad. Sci. USA 90: 755 759.
33. Egebjerg, J.,, V. Kukekov,, and S. F. Heinemann. 1994. Intron sequence directs RNA editing of the glutamate receptor subunit GluR2 coding sequence. Proc. Natl. Acad. Sci. USA 91: 10270 10274.
34. Gerber, A. Personal communication.
35. Gerber, A.,, M. A. O'Connell,, and W. Keller. 1997. Two forms of human double-stranded RNA-specific editase 1 (hREDl) generated by the insertion of an Alu cassette. RNA 3: 453 463.
36. Gilbertson, T. A.,, R. Scobey,, and M. Wison. 1991. Permeation of calcium ions through non-NMDA glutamate channels in retinal bipolar cells. Science 251: 1613 1615.
37. Grosjean, H. Personal communication.
38. Grosjean, H.,, S. Auxilien,, F. Constantinesco,, C. Simon,, Y. Corda,, H. F. Becker,, D. Foiret,, A. Morin,, Y. X. Jin,, M. Fournier,, and J. L. Fourrey. 1996. Enzymatic conversion of adenosine to inosine and to N1-methylinosine in transfer RNAs: a review. Biochimie 78: 488 501.
39. Hajjar, A. M.,, and M. L. Linial. 1995. Modification of retroviral RNA by double-stranded RNA adenosine deaminase. J. Virol. 69: 5878 5882.
40. Herb, A.,, M. Higuchi,, R. Sprengel,, and P. H. Seeburg. 1996. Q/ R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences. Proc. Natl. Acad. Sci. USA 93: 1875 1880.
41. Herbert, A.,, K. Lowenhaupt,, J. Spitzner,, and A. Rich. 1995. Chicken double-stranded RNA adenosine deaminase has apparent specificity for Z-DNA. Proc. Natl. Acad. Sci. USA 92: 7550 7554.
42. Herbert, A.,, J. Alfken,, Y. G. Kim,, I. S. Mian,, K. Nishikura,, and A. Rich. 1997. A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase. Proc. Natl. Acad. Sci. USA 94: 8421 8426.
43. Higuchi, M.,, F. N. Single,, M. Köhler,, B. Sommer,, R. Sprengel,, and P. H. Seeburg. 1993. RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. Cell 75: 1361 1370.
44. Holley, R. W.,, G. A. Everett,, J. T. Madison,, and A. Zamir. 1965. Nucleotide sequences in the yeast alanine transfer RNA. J. Biol. Chem. 240: 2122 2127.
45. Hollmann, M.,, A. O'Shea-Greenfield,, S. W. Rogers,, and S. Heinemann. 1989. Cloning by functional expression of a member of the glutamate receptor family. Nature 342: 643 648.
46. Hollmann, M.,, M. Hartley,, and S. Heinemann. 1991. Calcium permeability of kainate-AMPA-gated glutamate channels depends on subunit composition. Science 252: 851 854.
47. Hollmann, M.,, C. Maron,, and S. Heinemann. 1994. N-glycosylation site tagging suggests a three transmembrane domain topology for the glutamate receptor GluR1. Neuron 13: 1331 1343.
48. Hough, R. F.,, and B. L. Bass. 1994. Purification of the Xenopus laevis double-stranded RNA adenosine deaminase. J. Biol. Chem. 269: 9933 9939.
49. Hough, R. F.,, and B. L. Bass. 1997. Analysis of Xenopus dsRNA adenosine deaminase cDNAs reveals similarities to DNA methyltransferases. RNA 3: 356 370.
50. Hoyer, D.,, D. E. Clarke,, J. R. Fozard,, P. R. Hartig,, G. R. Martin,, E. J. Mylecharane,, P. R. Saxena,, and P. P. Humphrey. 1994. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol. Rev. 46: 157 203.
51. Hume, I. R.,, R. Dingledine,, and S. F. Heinemann. 1991. Identification of a site in glutamate receptor subunits that controls calcium permeability. Science 253: 1028 1031.
52. Hurst, S. R.,, R. F. Hough,, P. J. Aruscavage,, and B. L. Bass. 1995. Deamination of mammalian glutamate receptor RNA by Xenopus dsRNA adenosine deaminase: similarities to in vivo RNA editing. RNA 1: 1051 1060.
53. Jan, L. Y.,, and Y. N. Jan. 1997. Cloned potassium channels from eukaryotes and prokaryotes. Annu. Rev. Neurosci. 20: 91 123.
54. Jonas, P.,, and B. Sakmann. 1992. Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices. J. Physiol. 455: 143 147.
55. Jonas, P.,, C. Racca,, B. Sakmann,, P. H. Seburg,, and H. Monyer. 1994. Differences in Ca 2+ permeability of AMPA-type glutamate receptor channels in neocortical neurons caused by differential GluR-B subunit expression. Neuron 12: 1281 1289.
56. Julius, D. 1991. Molecular biology of serotonin receptors. Annu. Rev. Neurosci. 14: 335 360.
57. Julius, D.,, A. B. MacDermott,, R. Axel,, and T. M. Jessell. 1988. Molecular characterization of a functional cDNA encoding the serotonin 1c receptor. Science 241: 558 564.
58. Keinanen, K.,, W. Wisden,, B. Sommer,, P. Werner,, A. Herb,, T. A. Verdoorn,, B. Sakmann,, and P. H. Seeburg. 1990. A family of AMPA-selective glutamate receptors. Science 249: 556 560.
59. Kim, U.,, T. L. Garner,, T. Sanford,, D. Speicher,, J. M. Murray,, and K. Nishikura. 1994a. Purification and characterization of double-stranded RNA adenosine deaminase from bovine nuclear extracts. J. Biol. Chem. 269: 13480 13489.
60. Kim, U.,, Y. Wang,, T. Sanford,, Y. Zeng,, and K. Nishikura. 1994b. Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc. Natl. Acad. Sci. USA 91: 11457 11461.
61. Koh, D. S.,, J. R. P. Geiger,, P. Jonas,, and B. Sakmann. 1995. Ca 2+ permeable AMPA and NMDA receptor channels in basket cells of rat hippocampal dentate gyrus. J. Physiol. 485: 383 402.
62. Köhler, M.,, N. Burnashev,, B. Sakmann,, and P. H. Seeburg. 1993. Determinants of Ca 2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: diversity by RNA editing. Neuron 10: 491 500.
63. Kumar, M.,, and G. G. Carmichael. 1997. Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts. Proc. Natl. Acad. Sci. USA 94: 3542 3547.
64. Kuo, M. Y.-P.,, M. Chao,, and J. Taylor. 1989. Initiation of replication of the human hepatitis delta virus genome from clone DNA: role of delta antigen. J. Virol. 63: 1945 1950.
65. Lai, F.,, R. Drakas,, and K. Nishikura. 1995. Mutagenic analysis of double-stranded RNA adenosine deaminase, a candidate enzyme for RNA editing of glutamate-gated ion channel transcripts. J. Biol. Chem. 270: 17098 17105.
66. Lai, F.,, C. X. Chen,, K. C. Carter,, and K. Nishikura. 1997. Editing of glutamate receptor B subunit ion channel RNAs by four alternatively spliced DRADA2 double-stranded RNA adenosine deaminases. Mol. Cell. Biol. 17: 2413 2424.
67. Lino, M.,, S. Ozawa,, and K. Tsuzuki. 1990. Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurons. J. Physiol. 424: 151 165.
68. Liu, Y.,, C. X. George,, J. B. Patterson,, and C. E. Samuel. 1997. Functionally distinct double-stranded RNA-binding domains associated with alternative splice site variants of the interferon-inducible double-stranded RNA-specific adenosine deaminase. J. Biol. Chem. 272: 4419 4428.
69. Lomeli, H.,, J. Mosbacher,, T. Melcher,, T. Hoger,, J. R. P. Geiger,, T. Kuner,, H. Monyer,, M. Higuchi,, A. Bach,, and P. H. Seeburg. 1994. Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science 266: 1709 1713.
70. Luo, G.,, M. Chao,, S.-Y. Hsieh,, C. Sureau,, K. Nishikura,, and J. Taylor. 1990. A specific base transition occurs on replicating hepatitis delta virus RNA. J. Virol. 64: 1021 1027.
71. Ma, J.,, R. Qian,, F. M. Rausa,, and K. J. Colley. 1997. Two naturally occurring alpha2,6-sialyltransferase forms with a single amino acid change in the catalytic domain differ in their catalytic activity and proteolytic processing. J. Biol. Chem. 272: 672 679.
72. Maas, S.,, T. Melcher,, A. Herb,, P. H. Seeburg,, W. Keller,, S. Krause,, M. Higuchi,, and M. A. O'Connell. 1996. Structural requirements for RNA editing in glutamate receptor pre-mRNAs by recombinant double-stranded RNA adenosine deaminase. J. Biol. Chem. 271: 12221 12226.
73. Maas, S.,, T. Melcher,, and P. H. Seeburg. 1997. Mammalian RNA-dependent deaminases and edited mRNAs. Curr. Opin. Cell. Biol. 9: 343 349.
74. Melcher, T.,, S. Maas,, M. Higuchi,, W. Keller,, and P. H. Seeburg. 1995. Editing of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR-B pre-mRNA in vitro reveals site-selective adenosine to inosine conversion. J. Biol. Chem. 270: 8566 8570.
75. Melcher, T.,, S. Maas,, A. Herb,, R. Sprengel,, P. H. Seeburg,, and M. Higuchi. 1996a. A mammalian RNA editing enzyme. Nature 379: 460 464.
76. Melcher, T.,, S. Maas,, A. Herb,, R. Sprengel,, M. Higuchi,, and P. H. Seeburg. 1996b. RED2, a brain-specific member of the RNA-specific adenosine deaminase family. J. Biol. Chem. 271: 31795 31798.
77. Monyer, H.,, P. H. Seeburg,, and W. Wisden. 1991. Glutamate-operated channels: developmentally early and mature forms arise by alternative splicing. Neuron 6: 799 810.
78. Morse, D. P.,, and B. L. Bass. 1997. Detection of inosine in messenger RNA by inosine-specific cleavage. Biochemistry 36: 8429 8434.
79. Murphy, D. G.,, K. Dimock,, and C. Y. Rang. 1991. Numerous transitions in human parainfluenza virus 3 RNA recovered from persistently infected cells. Virology 181: 760 763.
80. Nakanishi, N.,, N. A. Shneider,, and R. Axel. 1990. A family of glutamate receptor genes: evidence for the formation of heteromultimeric receptors with distinct channel properties. Toxicon 28: 1333 1346.
81. Nishikura, K.,, C. Yoo,, U. Kim,, J. M. Murray,, P. A. Estes,, F. E. Cash,, and S. A. Liebhaber. 1991. Substrate specificity of the dsRNA unwinding/modifying activity. EMBO J. 10: 3523 3532.
82. O'Connell, M. A.,, and W. Keller. 1994. Purification and properties of double-stranded RNA-specific adenosine deaminase from calf thymus. Proc. Natl. Acad. Sci. USA 91: 10596 10600.
83. O'Connell, M. A.,, S. Krause,, M. Higuchi,, J. J. Hsuan,, N. F. Totty,, A. Jenny,, and W. Keller. 1995. Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. Mol. Cell. Biol. 15: 1389 1397.
84. O'Connell, M. A.,, A. Gerber,, and W. Keller. 1997. Purification of human double-stranded RNA-specific editase 1 (hRED1) involved in editing of brain glutamate receptor B pre-mRNA. J. Biol. Chem. 272: 473 478.
85. Ogura, A.,, K. Akita,, and Y. Kudo. 1990. Non-NMDA receptor mediates cytoplasmic calcium elevation in cultured hippocampal neurones. Neurosci. Res. 9: 103 113.
86. O'Hara, P. J.,, S. T. Nichol,, F. M. Horodyski,, and J. J. Holland. 1984. Vesicular stomatitis virus defective interfering particles can contain extensive genomic sequence rearrangements and base substitutions. Cell 36: 915 924.
87. Olney, J. W. 1990. Excitotoxic amino acids and neruopsychiatric disorders. Annu. Rev. Pharmacol. Toxicol. 30: 47 71.
88. Pandey, S. C.,, J. M. Davis,, and G. N. Pandey. 1995. Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates. J. Psychiatry Neurosci. 20: 215 225.
89. Patterson, J. B.,, and C. E. Samuel. 1995. Expression and regulation by interferon of a double-stranded-RNA-specific adenosine deaminase from human cells: evidence for two forms of the deaminase. Mol. Cell. Biol. 15: 5376 5388.
90. Patterson, J. B.,, D. C. Thomis,, S. L. Hans,, and C. E. Samuel. 1995. Mechanism of interferon action: double-stranded RNA-specific adenosine deaminase from human cells is inducible by alpha and gamma interferons. Virology 210: 508 511.
91. Patton, D. E.,, T. Silva,, and F. Bezanilla. 1997. RNA editing generates a diverse array of transcripts encoding squid Kv2 K + channels with altered functional properties. Neuron 19: 711 722.
92. Petschek, J. P.,, M. J. Mermer,, M. R. Scheckelhoff,, A. A. Simone,, and J. C. Vaughn. 1996. RNA editing in Drosophila 4f-rnp gene nuclear transcripts by multiple A-to-G conversions. J. Mol. Biol. 259: 885 890.
93. Pin, J. P.,, C. Joly,, S. F. Heinemann,, and J. Bockaert. 1994. Domains involved in the specificity of G protein activation in phospholipase C-coupled metabotropic glutamate receptors. EMBO J. 13: 342 348.
94. Pizzi, M.,, M. Ribola,, A. Valerio,, M. Memo,, and P. Spano. 1991. Various Ca2+ entry blockers prevent glutamate-induced neurotoxicity. Eur.J. Pharmacol. 209: 169 173.
95. Polson, A. G.,, P. F. Crain,, S. C. Pomerantz,, J. A. McCloskey,, and B. L. Bass. 1991. The mechanism of adenosine to inosine conversion by the double-stranded RNA unwinding/modifying activity: a high-performance liquid chromatography-mass spectrometry analysis. Biochemistry 30: 11507 11514.
96. Polson, A. G.,, and B. L. Bass. 1994. Preferential selection of adenosines for modification by double-stranded RNA adenosine deaminase. EMBO J. 13: 5701 5711.
97. Polson, A. G.,, B. L. Bass,, and J. L. Casey. 1996. RNA editing of hepatitis delta virus antigenome by dsRNA-adenosine deaminase. Nature 380: 454 456.
98. Ponzetto, A.,, P. J. Cote,, H. Popper,, B. H. Hoyer,, W. T. London,, E. C. Ford,, F. Bonino,, R. H. Purcell,, and J. L. Gerin. 1984. Transmission of the hepatitis B virus-associated δ agent to the eastern woodchuck. Proc. Natl. Acad. Sci. USA 81: 2208 2212.
99. Pruss, R. M.,, R. L. Akeson,, M. M. Racke,, and J. L. Wilburn. 1991. Agonist-activated cobalt uptake identifies divalent cation-permeable kainate receptors on neurones and glial cells. Neuron 7: 509 518.
100. Randall, R. D.,, and S. A. Thayer. 1992. Glutamate-induced calcium transient triggers delayed calcium overload and neurotoxicity in rat hippocampal neurons. J. Neurosci. 12: 1882 1895.
101. Rebagliati, M. R.,, and D. A. Melton. 1987. Antisense RNA injections in fertilized frog eggs reveal an RNA duplex unwinding activity. Cell 48: 599 605.
102. Rueda, P.,, B. Garcia-Barreno,, and J. A. Melero. 1994. Loss of conserved cysteine residues in the attachment (G) glycoprotein of two human respiratory syncytial virus escape mutants that contain multiple A-G substitutions (hypermutations). Virology 198: 653 662.
103. Rueter, S. M.,, C. M. Burns,, S. A. Coode,, P. Mookherjee,, and R. B. Emeson. 1995. Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine. Science 267: 1491 1494.
104. Ryu, W.-S.,, M. Bayer,, and J. Taylor. 1992. Assembly of hepatitis delta virus particles. J. Virol. 66: 2310 2315.
105. Saccomanno, L.,, and B. L Bass. 1994. The cytoplasm of Xenopus oocytes contains a factor that protects double-stranded RNA from adenosine-to-inosine modification. Mol. Cell. Biol. 14: 5425 5432.
106. Sakimura, K.,, H. Bujo,, E. Kushiya,, K. Araki,, M. Yamazaki,, H. Meguro,, A. Warashina,, S. Numa,, and M. Mishina. 1990. Functional expression from cloned cDNAs of glutamate receptor species responsive to kainate and quisqualate. FEBS Lett. 272: 73 80.
107. Scadden, A. D.,, and C. W. Smith. 1997. A ribonuclease specific for inosine-containing RNA: a potential role in antiviral defence? EMBO J. 16: 2140 2149.
108. Schumacher, J. M.,, K. Lee,, S. Edelhoff,, and R. E. Braun. 1995. Distribution of Tenr, an RNA-binding protein, in a lattice-like network within the spermatid nucleus in the mouse. Biol. Reprod. 52: 1274 1283.
109. Shih, T. M.,, and A. L. Goldin. 1997. Topology of the Shaker potassium channel probed with hydrophilic epitope insertions. J. Cell Biol. 136: 1037 1045.
110. Simpson, L.,, and R. B. Emeson. 1996. RNA editing. Annu. Rev. Neurosci. 19: 27 52.
111. Slesinger, P. A.,, Y. N. Jan,, and L. Y. Jan. 1993. The S4-S5 loop contributes to the ion-selective pore of potassium channels. Neuron 11: 739 749.
112. Sommer, B.,, K. Keinanen,, T. A. Verdoorn,, W. Wisden,, N. Burnashev,, A. Herb,, M. Köhler,, T. Takagi,, B. Sakmann,, and P. H. Seeburg. 1990. Flip and flop: a cell-specific functional switch in glutamate-operated channels of the CNS. Science 249: 1580 1585.
113. Sommer, B.,, M. Köhler,, R. Sprengel,, and P. H. Seeburg. 1991. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67: 11 19.
114. Tecott, L. H.,, L. M. Sun,, S. F. Akana,, A. M. Strack,, D. H. Lowenstein,, M. F. Dallman,, and D. Julius. 1995. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 374: 542 546.
115. Teitler, M.,, and K. Herrick-Davis. 1994. Multiple serotonin receptor subtypes: molecular cloning and functional expression. Crit. Rev. Neurobiol. 8: 175 188.
116. Verdoorn, T. A.,, N. Burnashev,, H. Monyer,, P. H. Seeburg,, and B. Sakmann. 1991. Structural determinants of ion flow through recombinant glutamate receptor channels. Science 252: 1715 718.
117. Wagner, R. W.,, and K. Nishikura. 1988. Cell cycle expression of RNA duplex unwindase activity in mammalian cells. Mol. Cell. Biol. 8: 770 777.
118. Wagner, R. W.,, J. E. Smith,, B. S. Cooperman,, and K. Nishikura. 1989. A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. Proc. Natl. Acad. Sci. USA 86: 2647 2651.
119. Wagner, R. W.,, C. Yoo,, L. Wrabetz,, J. Kamholz,, J. Buchhalter,, N. F. Hassan,, K. Khalili,, S. U. Kim,, B. Perussia,, and F. A. McMorris. 1990. Double-stranded RNA unwinding and modifying activity is detected ubiquitously in primary tissues and cell lines. Mol. Cell. Biol. 10: 5586 5590.
120. Wang, K.-S.,, Q.-L. Choo,, A. J. Weiner,, J.-H. Ou,, R. C. Najarian,, R. M. Thayer,, G. T. Mullenbach,, K. J. Denniston,, J. L. Gerin,, and M. Houghton. 1986. Structure, sequence and expression of the hepatitis delta viral genome. Nature 323: 508 513.
121. Wilson, R.,, R. Ainscough,, K. Anderson,, C. Baynes,, M. Berks,, J. Bonfield,, J. Burton,, M. Connell,, T. Copsey,, and J. Cooper. 1994. 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature 368: 32 38.
122. Wong, S. K.,, E. M. Parker,, and E. M. Ross. 1990. Chimeric muscarinic cholinergic: beta-adrenergic receptors that activate Gs in response to muscarinic agonists. J. Biol. Chem. 265: 6219 6224.
123. Wu, J.-C.,, P.-J. Chen,, M. Y.-P. Kuo,, S.-D. Lee,, D.-S. Chen,, and L.-P. Ting. 1991. Production of hepatitis delta virus and suppression of helper hepatitis B virus in a human hepatoma cell line. J. Virol. 65: 1099 1104.
124. Wu, T. T.,, H. J. Netter,, V. Bichko,, D. Lazinski,, and J. Taylor. 1994. RNA editing in the replication cycle of human hepatitis delta virus. Biochimie 76: 1205 1208.
125. Yang, J.-H.,, P. Sklar,, R. Axel,, and T. Maniatis. 1995. Editing of glutamate receptor subunit B pre-mRNA in vitro by site-specific deamination of adenosine. Nature 374: 77 81.
126. Yang, J. H.,, P. Sklar,, R. Axel,, and T. Maniatis. 1997. Purification and characterization of a human RNA adenosine deaminase for glutamate receptor B pre-mRNA editing. Proc. Natl. Acad. Sci. USA 94: 4354 4359.
127. Yellen, G.,, M. E. Jurman,, T. Abramson,, and R. MacKinnon. 1991. Mutations affecting internal TEA blockade identify the probable pore-forming region of a K+ channel. Science 251: 939 942.
128. Zheng, H.,, T.-B. Fu,, D. Lazinski,, and J. Taylor. 1992. Editing of the genomic RNA of human hepatitis delta virus. J. Virol. 66: 4693 4697.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error