A unique gene expression signature associated with serotonin 2C receptor RNA editing in the prefrontal cortex and altered in suicide

Human Molecular Genetics

Volumn 23, Issue 18, 2014, Pages 4801-4813

  Di Narzo, Antonio Fabio ^a   Kozlenkov, Alexey ^a,b   Roussos, Panos ^a,b   Hao, Ke ^a   Hurd, Yasmin ^a   Lewis, David A ^c   Sibille, Etienne ^c   Siever, Larry J ^a,b   Koonin, Eugene ^d   Dracheva, Stella ^a,b  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^d NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

SEROTONIN 2C RECEPTOR;

AUTOPSY; CASE CONTROL STUDY; COMPARATIVE STUDY; DNA METHYLATION; GENE EXPRESSION PROFILING; GENE REGULATORY NETWORK; GENETICS; HUMAN; MAJOR DEPRESSION; METABOLISM; NERVE CELL; PREFRONTAL CORTEX; RNA EDITING; SUICIDE;

AUTOPSY; CASE-CONTROL STUDIES; DEPRESSIVE DISORDER, MAJOR; DNA METHYLATION; GENE EXPRESSION PROFILING; GENE REGULATORY NETWORKS; HUMANS; NEURONS; PREFRONTAL CORTEX; RECEPTOR, SEROTONIN, 5-HT2C; RNA EDITING; SUICIDE;

EID: 84906839530     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddu195     Document Type: Article

References (75)

1. Giorgetti, M. and Tecott, L.H. (2004) Contributions of 5-HT(2C) receptors to multiple actions of central serotonin systems. Eur. J Pharmacol., 488, 1-9.
2. Millan, M.J. (2005) Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie, 60, 441-460.
3. Berg, K.A., Clarke, W.P., Cunningham, K.A. and Spampinato, U. (2008) Fine-tuning serotonin2c receptor function in the brain: molecular and functional implications. Neuropharmacology, 55, 969-976.
4. Werry, T.D., Loiacono, R., Sexton, P.M. and Christopoulos, A. (2008) RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function. Pharmacol. Ther., 119, 7-23.
5. Harvey, P.J., Li, X., Li, Y. and Bennett, D.J. (2006) Endogenous monoamine receptor activation is essential for enabling persistent sodium currents and repetitive firing in rat spinal motoneurons. J. Neurophysiol., 96, 1171-1186.
6. Gott, J.M. and Emeson, R.B. (2000) Functions and mechanisms of RNA editing. Annu. Rev. Genet., 34, 499-531.
7. Valente, L. and Nishikura, K. (2005) ADAR gene family and A-to-I RNA editing: diverse roles in posttranscriptional gene regulation. Prog. Nucleic Acid Res. Mol. Biol., 79, 299-338.
8. Athanasiadis, A., Rich, A. and Maas, S. (2004) Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLoS Biol., 2, e391.
9. Blow, M., Futreal, P.A., Wooster, R. and Stratton, M.R. (2004) A survey of RNA editing in human brain. Genome Res., 14, 2379-2387.
10. Levanon, E.Y., Eisenberg, E., Yelin, R., Nemzer, S., Hallegger, M., Shemesh, R., Fligelman, Z.Y., Shoshan, A., Pollock, S.R., Sztybel, D. et al. (2004) Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nat. Biotechnol., 22, 1001-1005.
11. Paz-Yaacov, N., Levanon, E.Y., Nevo, E., Kinar, Y., Harmelin, A., Jacob-Hirsch, J., Amariglio, N., Eisenberg, E. and Rechavi, G. (2010) Adenosine-to-inosine RNA editing shapes transcriptome diversity in primates. Proc. Natl. Acad. Sci. U. S. A, 107, 12174-12179.
12. Eisenberg, E., Nemzer, S., Kinar, Y., Sorek, R., Rechavi, G. and Levanon, E.Y. (2005) Is abundant A-to-I RNA editing primate-specific? Trends Genet., 21, 77-81.
13. Penn, A.C., Balik, A. and Greger, I.H. (2013) Reciprocal regulation of A-to-I RNA editing and the vertebrate nervous system. Front. Neurosci., 7, 61.
14. Rosenthal, J.J. and Seeburg, P.H. (2012) A-to-I RNA editing: effects on proteins key to neural excitability. Neuron, 74, 432-439.
15. Mattick, J.S. and Mehler, M.F. (2008) RNA editing, DNA recoding and the evolution of human cognition. Trends Neurosci., 31, 227-233.
16. Balik, A., Penn, A.C., Nemoda, Z. and Greger, I.H. (2013) Activity-regulated RNA editing in select neuronal subfields in hippocampus. Nucleic Acids Res., 41, 1124-1134.
17. Sanjana, N.E., Levanon, E.Y., Hueske, E.A., Ambrose, J.M. and Li, J.B. (2012) Activity-dependent A-to-I RNA editing in rat cortical neurons. Genetics, 192, 281-287.
18. Burns, C.M., Chu, H., Rueter, S.M., Hutchinson, L.K., Canton, H., Sanders-Bush, E. and Emeson, R.B. (1997) Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature, 387, 303-308.
19. Wang, Q., O'Brien, P.J., Chen, C.X., Cho, D.S., Murray, J.M. and Nishikura, K. (2000) Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors. J. Neurochem., 74, 1290-1300.
20. Moro, O., Lameh, J., Hogger, P. and Sadee, W. (1993) Hydrophobic amino acid in the i2 loop plays a key role in receptor-G protein coupling. J. Biol. Chem., 268, 22273-22276.
21. Dracheva, S., Elhakem, S.L., Marcus, S.M., Siever, L.J., McGurk, S.R. and Haroutunian, V. (2003) RNA editing and alternative splicing of human serotonin 2C receptor in schizophrenia. J. Neurochem., 87, 1402-1412.
22. Dracheva, S., Patel, N., Woo, D.A., Marcus, S.M., Siever, L.J. and Haroutunian, V. (2008) Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide. Mol. Psychiatry, 13, 1001-1010.
23. Lyddon, R., Dwork, A.J., Keddache, M., Siever, L.J. and Dracheva, S. (2013) Serotonin 2c receptorRNAediting in major depression and suicide. World J. Biol. Psychiatry, 14, 590-601.
24. Niswender, C.M., Copeland, S.C., Herrick-Davis, K., Emeson, R.B. and Sanders-Bush, E. (1999) RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J. Biol. Chem., 274, 9472-9478.
25. Du, Y., Davisson, M.T., Kafadar, K. and Gardiner, K. (2006) A-to-I pre-mRNA editing of the serotonin 2C receptor: comparisons among inbred mouse strains. Gene, 382:39-46.
26. Englander, M.T., Dulawa, S.C., Bhansali, P. and Schmauss, C. (2005) How stress and fluoxetine modulate serotonin 2C receptor pre-mRNA editing. J. Neurosci., 25, 648-651.
27. Zhu, H., Urban, D.J., Blashka, J., McPheeters, M.T., Kroeze, W.K., Mieczkowski, P., Overholser, J.C., Jurjus, G.J., Dieter, L., Mahajan, G.J. et al. (2012) Quantitative analysis of focused a-to-I RNA editing sites by ultra-high-throughput sequencing in psychiatric disorders. PLoS One., 7, e43227.
28. Murray, K.C., Nakae, A., Stephens, M.J., Rank, M., D'Amico, J., Harvey, P.J., Li, X., Harris, R.L., Ballou, E.W., Anelli, R. et al. (2010) Recovery of motoneuron and locomotor function after spinal cord injury depends on constitutive activity in 5-HT2C receptors. Nat. Med., 16, 694-700.
29. Niswender, C.M., Herrick-Davis, K., Dilley, G.E., Meltzer, H.Y., Overholser, J.C., Stockmeier, C.A., Emeson, R.B. and Sanders-Bush, E. (2001) RNA editing of the human serotonin 5-HT2C receptor. Alterations in suicide and implications for serotonergic pharmacotherapy. Neuropsychopharmacology, 24, 478-491.
30. Gurevich, I., Tamir, H., Arango, V., Dwork, A.J., Mann, J.J. and Schmauss, C. (2002) Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Neuron, 34, 349-356.
31. Iwamoto, K. and Kato, T. (2003) RNA editing of serotonin 2C receptor in human postmortem brains of major mental disorders. Neurosci. Lett., 346, 169-172.
32. Nock, M.K., Borges, G., Bromet, E.J., Cha, C.B., Kessler, R.C. and Lee, S. (2008) Suicide and suicidal behavior. Epidemiol. Rev., 30, 133-154.
33. Brent, D.A. and Mann, J.J. (2005) Family genetic studies, suicide, and suicidal behavior. Am. J. Med. Genet. C Semin. Med. Genet., 133C, 13-24.
34. Qin, P., Agerbo, E. and Mortensen, P.B. (2003) Suicide risk in relation to socioeconomic, demographic, psychiatric, and familial factors: a national register-based study of all suicides in Denmark, 1981-1997. Am. J Psychiatry, 160, 765-772.
35. Tsai, S.J., Hong, C.J. and Liou, Y.J. (2011) Recent molecular genetic studies and methodological issues in suicide research. Prog. Neuropsychopharmacol. Biol. Psychiatry, 35, 809-817.
36. Labonte, B. and Turecki, G. (2012) Epigenetic effects of childhood adversity in the brain and suicide risk. In Dwivedi, Y. (ed.), The Neurobiological Basis of Suicide. Boca Raton, FL, USA: CRC Press. Chapter 13.
37. Labonte, B. and Turecki, G. (2010) The epigenetics of suicide: explaining the biological effects of early life environmental adversity. Arch. Suicide Res., 14, 291-310.
38. Morabito, M.V., Ulbricht, R.J., O'Neil, R.T., Airey, D.C., Lu, P., Zhang, B., Wang, L. and Emeson, R.B. (2010) High-throughput multiplexed transcript analysis yields enhanced resolution of 5-hydroxytryptamine 2C receptor mRNA editing profiles. Mol. Pharmacol., 77, 895-902.
39. Lyddon, R., Dwork, A.J., Keddache, M., Siever, L.J. and Dracheva, S. (2013) Serotonin 2c receptorRNAediting in major depression and suicide. World J. Biol. Psychiatry, 14, 590-601.
40. Wu, L.G., Hamid, E., Shin, W. and Chiang, H.C. (2014) Exocytosis and endocytosis: modes, function, and coupling mechanisms. Annu. Rev. Physiol, 76, 301-331.
41. Labasque, M., Reiter, E., Becamel, C., Bockaert, J. and Marin, P. (2008) Physical interaction of calmodulin with the 5-hydroxytryptamine2C receptor C-terminus is essential for G protein-independent, arrestin-dependent receptor signaling. Mol. Biol. Cell, 19, 4640-4650.
42. Chen, C.X., Cho, D.S., Wang, Q., Lai, F., Carter, K.C. and Nishikura, K. (2000) A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single-and double-stranded RNA binding domains 1. RNA, 6, 755-767.
43. Le-Niculescu, H., Levey, D.F., Ayalew, M., Palmer, L., Gavrin, L.M., Jain, N., Winiger, E., Bhosrekar, S., Shankar, G., Radel, M. et al. (2013) Discovery and validation of blood biomarkers for suicidality. Mol. Psychiatry, 18, 1249-1264.
44. Kozlenkov, A., Roussos, P., Timashpolsky, A., Barbu, M., Rudchenko, S., Bibikova, M., Klotzle, B., Byne, W., Lyddon, R., Di Narzo, A.F. et al. (2014) Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites. Nucleic Acids Res., 42, 109-127.
45. Zhang, B. and Horvath, S. (2005) A general framework for weighted gene co-expression network analysis. Stat. Appl. Genet. Mol. Biol., 4, Article17.
46. Oldham, M.C., Konopka, G., Iwamoto, K., Langfelder, P., Kato, T., Horvath, S. and Geschwind, D.H. (2008) Functional organization of the transcriptome in human brain. Nat. Neurosci., 11, 1271-1282.
47. Sugino, K., Hempel, C.M., Miller, M.N., Hattox, A.M., Shapiro, P., Wu, C., Huang, Z.J. and Nelson, S.B. (2006) Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nat. Neurosci., 9, 99-107.
48. Lein, E.S., Hawrylycz, M.J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A.F., Boguski, M.S., Brockway, K.S., Byrnes, E.J. et al. (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature, 445, 168-176.
49. Winden, K.D., Oldham, M.C., Mirnics, K., Ebert, P.J., Swan, C.H., Levitt, P., Rubenstein, J.L., Horvath, S. and Geschwind, D.H. (2009) The organization of the transcriptional network in specific neuronal classes. Mol. Syst. Biol., 5, 291.
50. Cahoy, J.D., Emery, B., Kaushal, A., Foo, L.C., Zamanian, J.L., Christopherson, K.S., Xing, Y., Lubischer, J.L., Krieg, P.A., Krupenko, S.A. et al. (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci., 28, 264-278.
51. Miller, J.A., Horvath, S. and Geschwind, D.H. (2010) Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways. Proc. Natl. Acad. Sci. U. S. A, 107, 12698-12703.
52. Hawrylycz, M.J., Lein, E.S., Guillozet-Bongaarts, A.L., Shen, E.H., Ng, L., Miller, J.A., van de Lagemaat, L.N., Smith, K.A., Ebbert, A., Riley, Z.L. et al. (2012) An anatomically comprehensive atlas of the adult human brain transcriptome. Nature, 489, 391-399.
53. Voineagu, I., Wang, X., Johnston, P., Lowe, J.K., Tian, Y., Horvath, S., Mill, J., Cantor, R.M., Blencowe, B.J. and Geschwind, D.H. (2011) Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature, 474, 380-384.
54. Colantuoni, C., Lipska, B.K., Ye, T., Hyde, T.M., Tao, R., Leek, J.T., Colantuoni, E.A., Elkahloun, A.G., Herman, M.M., Weinberger, D.R. and Kleinman, J.E. (2011) Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature, 478, 519-523.
55. Ernst, C., McGowan, P.O., Deleva, V., Meaney, M.J., Szyf, M. and Turecki, G. (2008) The effects of pH on DNA methylation state: in vitro and post-mortem brain studies. J. Neurosci. Methods, 174, 123-125.
56. Lister, R., Mukamel, E.A., Nery, J.R., Urich, M., Puddifoot, C.A., Johnson, N.D., Lucero, J., Huang, Y., Dwork, A.J., Schultz, M.D. et al. (2013) Global epigenomic reconfiguration during mammalianbrain development. Science, 341, 1237905.
57. Fournier, A., Sasai, N., Nakao, M. and Defossez, P.A. (2012) The role of methyl-binding proteins in chromatin organization and epigenome maintenance. Brief. Funct. Genomics, 11, 251-264.
58. Kooistra, S.M. and Helin, K. (2012) Molecular mechanisms and potential functions of histone demethylases. Nat. Rev. Mol. Cell Biol., 13, 297-311.
59. Gavin, D.P., Chase, K.A. and Sharma, R.P. (2013) Active DNA demethylation in post-mitotic neurons: a reason for optimism. Neuropharmacology, 75, 233-245.
60. Huynh, J.L. and Casaccia, P. (2013) Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet Neurol., 12, 195-206.
61. Smith, P.G. and Day, N.E. (1984) The design of case-control studies: the influence of confounding and interaction effects. Int. J. Epidemiol., 13, 356-365.
62. Eran, A., Li, J.B., Vatalaro, K., McCarthy, J., Rahimov, F., Collins, C., Markianos, K., Margulies, D.M., Brown, E.N., Calvo, S.E. et al. (2013) Comparative RNA editing in autistic and neurotypical cerebella. Mol. Psychiatry, 18, 1041-1048.
63. Labonte, B., Suderman, M., Maussion, G., Navaro, L., Yerko, V., Mahar, I., Bureau, A., Mechawar, N., Szyf, M., Meaney, M.J. and Turecki, G. (2012) Genome-wide epigenetic regulation by early-life trauma. Arch. Gen. Psychiatry, 69, 722-731.
64. Orlandi, C., Barbon, A. and Barlati, S. (2012) Activity regulation of adenosine deaminases acting on RNA (ADARs). Mol. Neurobiol., 45, 61-75.
65. Higuchi, M., Maas, S., Single, F.N., Hartner, J., Rozov, A., Burnashev, N., Feldmeyer, D., Sprengel, R. and Seeburg, P.H. (2000) Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature, 406, 78-81.
66. Abbas, A.I., Urban, D.J., Jensen, N.H., Farrell, M.S., Kroeze, W.K., Mieczkowski, P., Wang, Z. and Roth, B.L. (2010) Assessing serotonin receptor mRNA editing frequency by a novel ultra high-throughput sequencing method. Nucleic Acids Res., 38, e118.
67. Nikoshkov, A., Drakenberg, K., Wang, X., Horvath, M.C., Keller, E. and Hurd, Y.L. (2008) Opioid neuropeptide genotypes in relation to heroin abuse: dopamine tone contributes to reversed mesolimbic proenkephalin expression. Proc. Natl. Acad. Sci. U. S. A, 105, 786-791.
68. Drakenberg, K., Nikoshkov, A., Horvath, M.C., Fagergren, P., Gharibyan, A., Saarelainen, K., Rahman, S., Nylander, I., Bakalkin, G., Rajs, J. et al. (2006) Muopioid receptor A118Gpolymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers. Proc. Natl. Acad. Sci. U. S. A, 103, 7883-7888.
69. Guilloux, J.P., Douillard-Guilloux, G., Kota, R., Wang, X., Gardier, A.M., Martinowich, K., Tseng, G.C., Lewis, D.A. and Sibille, E. (2012) Molecular evidence for BDNF-and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol. Psychiatry, 17, 1130-1142.
70. Tripp, A., Oh, H., Guilloux, J.P., Martinowich, K., Lewis, D.A. and Sibille, E. (2012) Brain-derived neurotrophic factor signaling and subgenual anterior cingulate cortex dysfunction in major depressive disorder. Am. J. Psychiatry, 169, 1194-1202.
71. Navarrett, S., Collier, L., Cardozo, C. and Dracheva, S. (2012) Alterations of serotonin 2C and 2A receptors in response to T10 spinal cord transection in rats. Neurosci. Lett., 506, 74-78.
72. Roberts, A., Trapnell, C., Donaghey, J., Rinn, J.L. and Pachter, L. (2011) Improving RNA-Seq expression estimates by correcting for fragment bias. Genome Biol., 12, R22.
73. Wang, X., Lin, Y., Song, C., Sibille, E. and Tseng, G.C. (2012) Detecting disease-associated genes with confounding variable adjustment and the impact on genomic meta-analysis: with application to major depressive disorder. BMC Bioinformatics, 13, 52.
74. Bibikova, M., Le, J., Barnes, B., Saedinia-Melnyk, S., Zhou, L., Shen, R. and Gunderson, K.L. (2009) Genome-wide DNA methylation profiling using Infinium(R) assay. Epigenomics, 1, 177-200.
75. Bibikova, M., Barnes, B., Tsan, C., Ho, V., Klotzle, B., Le, J.M., Delano, D., Zhang, L., Schroth, G.P., Gunderson, K.L. et al. (2011) High density DNA methylation array with single CpG site resolution. Genomics, 98, 288-295.