Ronald B. Emeson, Ph.D.
Vanderbilt University Medical Center
8160B MRB III
Nashville, TN 37232-8548
The research interests of our laboratory focus on the field of molecular neurobiology. By integrating the disciplines of peptide biochemistry, cell biology, animal physiology and molecular biology, we hope to gain a better understanding of the cellular and molecular processes underlying neuronal communication in normal and pathophysiological disease states.
Our laboratory is examining the molecular mechanisms involved in the editing of numerous RNA transcripts in the mammalian central nervous system. RNA editing is a post-transcriptional modification in which specific adenosine residues are converted to inosine moieties (A-to-I editing) via the actions of double-stranded RNA-specific adenosine deaminases. As a result of these deamination events, the coding potential of RNAs can be subtly altered to change as little as a single amino acid residue in resultant proteins. In the case of glutamate-gated ion channels, RNA editing can dramatically alter both the ion permeation and electrophysiological properties of these ionotropic receptors. Since glutamate-gated channels are critically involved in processes of excitatory neurotransmission, slight alterations in RNA editing patterns have profound effects upon the normal neurophysiology of the brain. RNA editing events within the 2C-subtype of serotonin receptor can modulate the efficacy by which this seven transmembrane-spanning receptor can couple to its specific intracellular signaling pathways. Since this serotonin receptor has been implicated in a number of neuropsychiatric disease states, including depression and schizophrenia, aberrant RNA editing patterns may play an important role in the etiology of these disorders. Recent studies from our laboratory have also demonstrated that overexpression of ADAR2, a double-stranded RNA-specific adenosine deaminase that catalyzes A-to-I editing results in excessive obesity in transgenic mice, suggesting that misregulation of this post-transcriptional modification can result in severe pathophysiological defects. Current research efforts in the laboratory focus upon the regulation of RNA editing as well as biochemical and bioinformatics strategies for the identification of additional RNAs that are substrates for this type of RNA processing event.
- Anastasio, NC, Stutz, SJ, Fox, RG, Sears, RM, Emeson, RB, DiLeone, RJ, O''Neil, RT, Fink, LH, Li, D, Green, TA, Moeller, FG, Cunningham, KA Functional status of the serotonin 5-HT2C receptor (5-HT2CR) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence. Neuropsychopharmacology, 39(2), 370-82, 2014.
- Ulbricht, RJ, Emeson, RB One hundred million adenosine-to-inosine RNA editing sites: Hearing through the noise. Bioessays, 36(8), 730-5, 2014.
- Hood, JL, Morabito, MV, Martinez, CR, Gilbert, JA, Ferrick, EA, Ayers, GD, Chappell, JD, Dermody, TS, Emeson, RB Reovirus-mediated induction of ADAR1 (p150) minimally alters RNA editing patterns in discrete brain regions. Mol Cell Neurosci, 61C97-109, 2014.
- Hood, JL, Emeson, RB Editing of Neurotransmitter Receptor and Ion Channel RNAs in the Nervous System. Curr Top Microbiol Immunol, 2011.
- O''Neil, RT, Emeson, RB Quantitative analysis of 5HT(2C) receptor RNA editing patterns in psychiatric disorders. Neurobiol Dis, 2011.
- Morabito, MV, Ulbricht, RJ, O''Neil, RT, Airey, DC, Lu, P, Zhang, B, Wang, L, Emeson, RB High-throughput multiplexed transcript analysis yields enhanced resolution of 5-hydroxytryptamine 2C receptor mRNA editing profiles. Mol Pharmacol, 77(6), 895-902, 2010.
- Olaghere da Silva, UB, Morabito, MV, Canal, CE, Airey, DC, Emeson, RB, Sanders-Bush, E Impact of RNA Editing on Functions of the Serotonin 2C Receptor in vivo. Front Neurosci, 426, 2010.
- Morabito, MV, Abbas, AI, Hood, JL, Kesterson, RA, Jacobs, MM, Kump, DS, Hachey, DL, Roth, BL, Emeson, RB Mice with altered serotonin 2C receptor RNA editing display characteristics of Prader-Willi syndrome. Neurobiol Dis, 39169-80, 2010.
- Stefl, R, Oberstrass, FC, Hood, JL, Jourdan, M, Zimmermann, M, Skrisovska, L, Maris, C, Peng, L, Hofr, C, Emeson, RB, Allain, FH The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence-specific readout of the minor groove. Cell, 143(2), 225-37, 2010.
- Jacobs, MM, Fogg, RL, Emeson, RB, Stanwood, GD ADAR1 and ADAR2 expression and editing activity during forebrain development. Dev Neurosci, 31(3), 223-37, 2009.
- Morabito, MV, Emeson, RB RNA editing as a therapeutic target for CNS disorders. Neuropsychopharmacology, 34(1), 246, 2009.
- Rula, EY, Lagrange, AH, Jacobs, MM, Hu, N, Macdonald, RL, Emeson, RB Developmental modulation of GABA(A) receptor function by RNA editing. J Neurosci, 28(24), 6196-201, 2008.
- Singh, M, Kesterson, RA, Jacobs, MM, Joers, JM, Gore, JC, Emeson, RB Hyperphagia-mediated Obesity in Transgenic Mice Misexpressing the RNA-editing Enzyme ADAR2. J Biol Chem, 282(31), 22448-59, 2007.
- Rula, EY, Emeson, RB Mouse Models to Elucidate the Functional Roles of Adenosine-to-Inosine Editing. Methods Enzymol, 424333-67, 2007.
- Thompson, BJ, Washington, MK, Kurre, U, Singh, M, Rula, EY, Emeson, RB Protective Roles of alpha-Calcitonin and beta-Calcitonin Gene-Related Peptide in Spontaneous and Experimentally Induced Colitis. Dig Dis Sci, 2007.
- Feng, Y, Sansam, CL, Singh, M, Emeson, RB Altered RNA editing in mice lacking ADAR2 autoregulation. Mol Cell Biol, 26(2), 480-8, 2006.
- Huebner, AK, Schinke, T, Priemel, M, Schilling, S, Schilling, AF, Emeson, RB, Rueger, JM, Amling, M Calcitonin deficiency in mice progressively results in high bone turnover. J Bone Miner Res, 21(12), 1924-34, 2006.
- Stefl, R, Xu, M, Skrisovska, L, Emeson, RB, Allain, FH Structure and Specific RNA Binding of ADAR2 Double-Stranded RNA Binding Motifs. Structure, 14(2), 345-55, 2006.
- Xu, M, Wells, KS, Emeson, RB Substrate-dependent Contribution of Double-stranded RNA-binding Motifs to ADAR2 Function. Mol Biol Cell, 17(7), 3211-20, 2006.
- Emeson, RB, Morabito, MV Food fight: the NPY-serotonin link between aggression and feeding behavior. Sci STKE, 2005(277), pe12, 2005.
- Stefl, R, Skrisovska, L, Xu, M, Emeson, RB, Allain, FH Resonance assignments of the double-stranded RNA-binding domains of adenosine deaminase acting on RNA 2 (ADAR2). J Biomol NMR, 31(1), 71-2, 2005.
- Sansam, CL and RB Emeson "mRNA Editing." In: Encyclopedia of Life Sciences, John Wiley & Sons, Ltd: Chichester [doi:10.1038/npg.els.0005041] , 2005.
- Schinke, T, Liese, S, Priemel, M, Haberland, M, Schilling, AF, Catala-Lehnen, P, Blicharski, D, Rueger, JM, Gagel, RF, Emeson, RB, Amling, M Decreased bone formation and osteopenia in mice lacking alpha-calcitonin gene-related peptide. J Bone Miner Res, 19(12), 2049-56, 2004.
- Dawson, T. Renee, Sansam, Christopher L., Emeson, Ronald B. Structure and sequence determinants required for the editing of ADAR2 substrates. J Biol Chem, 2794941-4951, 2004.
- Maison, SF, Emeson, RB, Adams, JC, Luebke, AE, Liberman, MC Loss of alpha CGRP reduces sound-evoked activity in the cochlear nerve. J Neurophysiol, 90(5), 2941-9, 2003.
- Sansam, Christopher L, Wells, K Sam, Emeson, Ronald B Modulation of RNA editing by functional nucleolar sequestration of ADAR2. Proc Natl Acad Sci U S A, 100(24), 14018-23, 2003.
- El Meskini, R, Jin, L, Marx, R, Bruzzaniti, A, Lee, J, Emeson, R, Mains, R A signal sequence is sufficient for green fluorescent protein to be routed to regulated secretory granules. Endocrinology, 142(2), 864-73, 2001.
- Niswender, C M, Herrick-Davis, K, Dilley, G E, Meltzer, H Y, Overholser, J C, Stockmeier, C A, Emeson, R B, Sanders-Bush, E RNA editing of the human serotonin 5-HT2C receptor. alterations in suicide and implications for serotonergic pharmacotherapy. Neuropsychopharmacology, 24(5), 478-91, 2001.
- Berg, KA, Cropper, JD, Niswender, CM, Sanders-Bush, E, Emeson, RB, Clarke, WP RNA-editing of the 5-HT(2C) receptor alters agonist-receptor-effector coupling specificity. Br J Pharmacol, 134(2), 386-92, 2001.
- Singh M and Emeson RB "Adenosine to Inosine RNA Editing: Substrates and Consequences." RNA Editing: Frontiers in Molecular Biology. (BL Bass, ed.) Oxford University Press:London, 109-138, 2000.
- Gott, JM, Emeson, RB Functions and mechanisms of RNA editing. Annu Rev Genet, 34499-531, 2000.
- Lu, J T, Son, Y J, Lee, J, Jetton, T L, Shiota, M, Moscoso, L, Niswender, K D, Loewy, A D, Magnuson, M A, Sanes, J R, Emeson, R B Mice lacking alpha-calcitonin gene-related peptide exhibit normal cardiovascular regulation and neuromuscular development. Mol Cell Neurosci, 14(2), 99-120, 1999.
- Niswender, CM, Copeland, SC, Herrick-Davis, K, Emeson, RB, Sanders-Bush, E RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J Biol Chem, 274(14), 9472-8, 1999.
- Rueter, S M, Dawson, T R, Emeson, R B Regulation of alternative splicing by RNA editing. Nature, 399(6731), 75-80, 1999.
- Liu, Y, Emeson, RB, Samuel, CE 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. J Biol Chem, 274(26), 18351-8, 1999.
- Rueter S and RB Emeson "Adenosine to Inosine Conversion in mRNA." Modification and editing of RNA: the alteration of RNA structure and function. (H. Grosjean and R. Benne, eds.) ASM Press:East Norwalk, CT, 343-361, 1998.
- Sanes, J.R., E.D. Apel, R.W. Burgess, R.B. Emeson, G. Feng, M. Gautam, D. Glass, R.M. Grady, E. Krejci, J.W. Lichtman, J.T. Lu, J. Massoulie, J.H. Miner, L.M. Moscoso, Q. Nguyen, M. Nichol, P.G. Noakes, B.L. Patton, Y.J. Son, G.D. Yancopoulos and H. Zhou "Development of the neuromuscular junction: genetic analysis in mice." J Physiol Paris , 92167 172, 1998.
- Niswender, C M, Sanders-Bush, E, Emeson, R B Identification and characterization of RNA editing events within the 5-HT2C receptor. Ann N Y Acad Sci, 86138-48, 1998.
- Bass, BL, Nishikura, K, Keller, W, Seeburg, PH, Emeson, RB, O''Connell, MA, Samuel, CE, Herbert, A A standardized nomenclature for adenosine deaminases that act on RNA. RNA, 3(9), 947-9, 1997.
- Burns, C M, Chu, H, Rueter, S M, Hutchinson, L K, Canton, H, Sanders-Bush, E, Emeson, R B Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature, 387(6630), 303-8, 1997.
- Breyer, R M, Emeson, R B, Davis, L S, Breyer, M D "Structure and localization of the rabbit prostaglandin EP3 receptor." Adv Exp Med Biol, 400A261-8, 1997.
- Canton, H, Emeson, R B, Barker, E L, Backstrom, J R, Lu, J T, Chang, M S, Sanders-Bush, E Identification, molecular cloning, and distribution of a short variant of the 5-hydroxytryptamine2C receptor produced by alternative splicing. Mol Pharmacol, 50(4), 799-807, 1996.
- Emeson, R.B "Post-transcriptional regulation of calcitonin gene-related peptide (CGRP) mRNA production." Neurogenic Inflammation. (P. Geppetti and P. Holzer, eds.), CRC Press, Boca Raton, FL, 15-30, 1996.
- Simpson, L, Emeson, RB RNA editing. Annu Rev Neurosci, 1927-52, 1996.
- Rueter, S M, Burns, C M, Coode, S A, Mookherjee, P, Emeson, R B Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine. Science, 267(5203), 1491-4, 1995.
- Breyer, RM, Emeson, RB, Tarng, JL, Breyer, MD, Davis, LS, Abromson, RM, Ferrenbach, SM Alternative splicing generates multiple isoforms of a rabbit prostaglandin E2 receptor. J Biol Chem, 269(8), 6163-9, 1994.
- Yeakley, JM, Hedjran, F, Morfin, JP, Merillat, N, Rosenfeld, MG, Emeson, RB Control of calcitonin/calcitonin gene-related peptide pre-mRNA processing by constitutive intron and exon elements. Mol Cell Biol, 13(10), 5999-6011, 1993.
- Rosenfeld, MG, Emeson, RB, Yeakley, JM, Merillat, N, Hedjran, F, Lenz, J, Delsert, C Calcitonin gene-related peptide: a neuropeptide generated as a consequence of tissue-specific, developmentally regulated alternative RNA processing events. Ann N Y Acad Sci, 6571-17, 1992.
- Emeson, RB, Yeakley, JM, Hedjran, F, Merillat, N, Lenz, HJ, Rosenfeld, MG Posttranscriptional regulation of calcitonin/CGRP gene expression. Ann N Y Acad Sci, 65718-35, 1992.
- Emeson, RB, Hedjran, F, Yeakley, JM, Guise, JW, Rosenfeld, MG Alternative production of calcitonin and CGRP mRNA is regulated at the calcitonin-specific splice acceptor. Nature, 341(6237), 76-80, 1989.
- Rosenfeld, M, Crenshaw, E B, Emeson, R, Leff, S, Guise, J, Lira, S, Nelson, C, Nelson, C, Russo, A Transcriptional and post-transcriptional strategies in neuroendocrine gene expression. Dev Biol (N Y 1985), 5317-34, 1988.
- Emeson, RB, Eipper, BA Characterization of pro-ACTH/endorphin-derived peptides in rat hypothalamus. J Neurosci, 6(3), 837-49, 1986.
- Emeson, RB Hypothalamic peptidyl-glycine alpha-amidating monooxygenase: preliminary characterization. J Neurosci, 4(10), 2604-13, 1984.