title: BC1 regulation of metabotropic glutamate receptor-mediated neuronal excitability.
abstract: Regulatory RNAs have been suggested to contribute to the control of gene expression in eukaryotes. Brain cytoplasmic (BC) RNAs are regulatory RNAs that control translation initiation. We now report that neuronal BC1 RNA plays an instrumental role in the protein-synthesis-dependent implementation of neuronal excitation-repression equilibria. BC1 repression counter-regulates translational stimulation resulting from synaptic activation of group I metabotropic glutamate receptors (mGluRs). Absence of BC1 RNA precipitates plasticity dysregulation in the form of neuronal hyperexcitability, elicited by group I mGluR-stimulated translation and signaled through the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway. Dysregulation of group I mGluR function in the absence of BC1 RNA gives rise to abnormal brain function. Cortical EEG recordings from freely moving BC1(-/-) animals show that group I mGluR-mediated oscillations in the gamma frequency range are significantly elevated. When subjected to sensory stimulation, these animals display an acute group I mGluR-dependent propensity for convulsive seizures. Inadequate RNA control in neurons is thus causally linked to heightened group I mGluR-stimulated translation, neuronal hyperexcitability, heightened gamma band oscillations, and epileptogenesis. These data highlight the significance of small RNA control in neuronal plasticity.
authors.affiliation: The Robert F. Furchgott Center for Neural and Behavioral Science, Department of Physiology and Pharmacology, State University of New York, Brooklyn, 11203, USA. jzhong@downstate.edu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhong
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Chuang
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bianchi
authors.forename: Wangfa
authors.initials: W
authors.lastname: Zhao
authors.forename: Heekyung
authors.initials: H
authors.lastname: Lee
authors.forename: André A
authors.initials: AA
authors.lastname: Fenton
authors.forename: Robert K S
authors.initials: RK
authors.lastname: Wong
authors.forename: Henri
authors.initials: H
authors.lastname: Tiedge
mesh_terms: D000200:Action Potentials; D000818:Animals; D001921:Brain / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D004569:Electroencephalography; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000096:biosynthesis; D051528:Guanylate Kinases; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010507:Periodicity; D020733:RNA, Small Cytoplasmic / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012640:Seizures / Q000503:physiopathology; D013569:Synapses / Q000502:physiology
chemical_list: D000076122:Disks Large Homolog 4 Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020733:RNA, Small Cytoplasmic; D018094:Receptors, Metabotropic Glutamate; C117734:BC1 RNA; C501447:Dlg4 protein, mouse; C497684:Fmr1 protein, mouse
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):734-9
references.pmid: 18184799
references.citation: Epilepsia. 2000 Jan;41(1):19-23
references.pmid: 10643918
references.citation: J Neurosci. 2008 Jan 9;28(2):543-7
references.pmid: 18184796
references.citation: J Neurophysiol. 2002 Mar;87(3):1395-403
references.pmid: 11877514
references.citation: J Neurosci. 2002 Dec 1;22(23):10232-41
references.pmid: 12451124
references.citation: Neuron. 2005 Oct 6;48(1):13-6
references.pmid: 16273717
references.citation: J Neurosci. 2006 Jul 5;26(27):7151-5
references.pmid: 16822971
references.citation: Annu Rev Neurosci. 2006;29:77-103
references.pmid: 16776580
references.citation: Mol Cell Biol. 2008 May;28(9):3008-19
references.pmid: 18316401
references.citation: J Neurosci. 2004 Oct 20;24(42):9425-33
references.pmid: 15496678
references.citation: J Cell Biol. 2006 Nov 6;175(3):427-39
references.pmid: 17074884
references.citation: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5395-400
references.pmid: 9144248
references.citation: Annu Rev Cell Dev Biol. 2005;21:223-45
references.pmid: 16212494
references.citation: Nature. 1995 Feb 16;373(6515):612-5
references.pmid: 7854418
references.citation: Neuron. 2003 Feb 6;37(3):417-31
references.pmid: 12575950
references.citation: Hum Mol Genet. 2003 Dec 15;12(24):3295-305
references.pmid: 14570712
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7080-5
references.pmid: 11416191
references.citation: Trends Genet. 2005 May;21(5):287-8
references.pmid: 15851065
references.citation: Neurochem Res. 2002 Oct;27(10):1065-77
references.pmid: 12462405
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13357-62
references.pmid: 15329415
references.citation: Semin Cell Dev Biol. 2007 Apr;18(2):216-23
references.pmid: 17331761
references.citation: Genes Brain Behav. 2004 Dec;3(6):337-59
references.pmid: 15544577
references.citation: Neuron. 2001 Nov 20;32(4):683-96
references.pmid: 11719208
references.citation: Neuron. 2002 Jan 31;33(3):325-40
references.pmid: 11832222
references.citation: Electroencephalogr Clin Neurophysiol. 1969 Apr;26(4):407-18
references.pmid: 4183562
references.citation: Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7168-71
references.pmid: 8102206
references.citation: J Neurophysiol. 2002 Oct;88(4):1625-33
references.pmid: 12364493
references.citation: Cell. 2003 Feb 7;112(3):317-27
references.pmid: 12581522
references.citation: Sci STKE. 2006 Oct 10;2006(356):re12
references.pmid: 17033045
references.citation: J Neurosci. 2005 Aug 31;25(35):8048-55
references.pmid: 16135762
references.citation: J Neurosci. 2004 Aug 18;24(33):7272-6
references.pmid: 15317853
references.citation: Bioessays. 2003 Oct;25(10):930-9
references.pmid: 14505360
references.citation: Mol Biol Rep. 1994 May;19(3):195-200
references.pmid: 7969107
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14374-8
references.pmid: 14614133
references.citation: J Neurosci. 2006 Sep 13;26(37):9560-6
references.pmid: 16971540
references.citation: Trends Neurosci. 2004 Jul;27(7):370-7
references.pmid: 15219735
references.citation: J Neurosci. 1993 Sep;13(9):4054-63
references.pmid: 8396172
references.citation: J Neurophysiol. 1998 Aug;80(2):989-93
references.pmid: 9705485
references.citation: Nat Neurosci. 1998 Nov;1(7):602-9
references.pmid: 10196568
references.citation: EMBO Rep. 2006 Jan;7(1):31-5
references.pmid: 16391534
references.citation: Nat Rev Neurosci. 2001 Dec;2(12):889-98
references.pmid: 11733796
references.citation: J Neurophysiol. 1997 Jul;78(1):539-44
references.pmid: 9242303
references.citation: J Neurosci. 2001 Feb 1;21(3):983-98
references.pmid: 11157084
references.citation: Neuron. 2006 Oct 5;52(1):155-68
references.pmid: 17015233
references.citation: Mol Cell Biol. 2003 Sep;23(18):6435-41
references.pmid: 12944471
references.citation: Science. 2000 May 19;288(5469):1254-7
references.pmid: 10818003
references.citation: RNA Biol. 2005 Jan;2(1):1-3
references.pmid: 17132937
references.citation: J Gen Physiol. 2000 Aug;116(2):191-209
references.pmid: 10919866
references.citation: J Neurophysiol. 2006 May;95(5):3291-5
references.pmid: 16452252
references.citation: Behav Brain Res. 2004 Sep 23;154(1):273-89
references.pmid: 15302134
references.citation: J Neurosci. 2005 May 18;25(20):5087-95
references.pmid: 15901791
references.citation: Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17504-9
references.pmid: 15548614
references.citation: BMC Neurosci. 2006 Feb 17;7:17
references.pmid: 16503994
references.citation: J Cell Biol. 2005 Dec 5;171(5):811-21
references.pmid: 16330711
references.citation: Neuroscientist. 2004 Oct;10(5):456-66
references.pmid: 15487031
references.citation: J Mol Biol. 2005 Oct 14;353(1):88-103
references.pmid: 16154588
references.citation: J Neurosci. 2006 Jul 5;26(27):7147-50
references.pmid: 16822970
references.citation: J Neurosci. 2006 Jan 4;26(1):158-68
references.pmid: 16399683
references.citation: J Neurosci. 2001 Aug 15;21(16):6387-94
references.pmid: 11487662
references.citation: Neuropharmacology. 2005 Dec;49(7):1053-66
references.pmid: 16054174
references.citation: J Cell Biol. 2007 Apr 9;177(1):7-11
references.pmid: 17420288
references.citation: Mol Cell Biol. 2003 Dec;23(24):8925-33
references.pmid: 14645505
references.citation: Neuroscience. 2001;103(4):1043-50
references.pmid: 11301211
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4667-72
references.pmid: 15070775