Summary
The term “RNA editing” is used to identify any mechanism responsible for producing mRNA molecules with sequence information not specifically encoded in the DNA.
RNA editing is therefore an important event in gene modification, which takes place at a post-transcriptional level. The molecular mechanism of RNA editing involves site-selective deamination of adenosine to inosine in pre-mRNA, which leads to altering translation codons and splicing in nuclear transcripts, whereby functionally distinct proteins can be produced from a single gene. The mammalian editing enzymes ADARs (adenosine deaminases acting on RNA) are widely expressed in brain and other tissues: however, up until now their substrates have mainly been found in the Central Nervous System (CNS). Of particular relevance in the CNS is the editing occurring at the ionotropic glutamate receptors (GluRs) level. Three AMPA and two Kainate receptors are subject to RNA editing. The consequence of this process is the substitution of specific amino acids in functionally critical positions of the receptors. Depending on the GluR involved, the consequences of editing will involve: activation and/or inhibition of splicing sites; modulation of the trafficking of the receptor to the plasma membrane; the process of tetramerization of the receptor subunits; modification of the ions passage through the receptor channel; modulation of the desensitization and action potential recovery times. All these events are specific to the different GluRs and are genetically and developmentally controlled.
RNA editing is therefore a crucial event involved in controlling transmission of the action potential at the postsynaptic level. This modulation involves the transmission of all sensory stimuli to the CNS and gives rise to the “Sensotype”. The Sensotype therefore defines the “way” in which the information acquired from the environment by the sensory systems is transmitted to the brain. The signals and inputs deriving from the Sensotype are transmitted to the brain, which processes and stores these signals thus generating the “Brainotype”. Brainotype and Sensotype are genetically and environmentally determined; they are individually unique and specific to every living organism with a nervous system. Their characteristics are, at least in part, dependent on the modulation of the “RNA editing” process since glutamate receptors represent the main neurotransmitter system in the CNS.
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References
Akbarian S, Smith MA, Jones EG (1995) Editing for an AMPA receptor subunit RNA in prefrontal cortex and striatum in Alzheimer’s disease, Huntington’s disease and schizophrenia. Brain Res 699(2): 297–304
Bass BL (2002) RNA Editing by adenosine deaminase that Act on RNA. Ann Rev Biochem 71: 817–846
Barbon A, Barlati S (2000) Genomic organization, proposed alternative splicing mechanisms, and RNA editing structure of GRIK1 gene. Cytogenetics Cell Genetics 88: 236–239
Barbon A, Vallini I, Barlati S (2001) Genomic organization of the human GRIK2 gene and evidence for multiple splicing variants. Gene 274: 187–197
Barbon A, Vallini I, La Via L, Marchina E, Barlati S (2003) Glutamate receptor RNA editing: a molecular analysis of GluR2, GluR5 and GluR6 in human brain tissues and in NT2 cells following in vitro neural differentiation. Brain Res Mol Brain Res 117(2): 168–178
Benne R, Van den Burg J, Brakenhoff JP, Sloof P, Van Boom JH, Tromp MC (1986) Major transcript of the frameshifted coxII gene from trypanosoma mitochondria contains four nucleotides that are not encoded in the DNA. Cell 46: 819–826
Bernard A, Khrestchatisky M (1994) Assessing the extent of RNA editing in the TMII regions of GluR5 and GluR6 kainate receptors during rat brain development. J Neurochem 62: 2057–2060
Bernard A, Ferhat L, Dessi F, Charton G, Represa A, Ben-Ari Y, Khrestchatisky M (1999) Q/R editing of the rat GluR5 and GluR6 kainate receptors in vivo and in vitro: evidence for independent developmental, pathological and cellular regulation. Eur J Neurosci 11: 604–616
Bigge, CF (1999) Ionotropic glutamate receptors. Curr Opin in Chem Biol 3: 441–447
Brusa R, Zimmermann F, Koh DS, Feldmeyer D, Gass P, Seeburg PH, Sprengel R (1995) Early-onset epilepsy and postnatal lethality associated with an editing-deficient GluR-B allele in mice. Science 270: 1677–1680
Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51: 1–61
Egebjerg J, Heinemann SF (1993) Ca2+ permeability of unedited and edited versions of the kainate selective glutamate receptor GluR6. Proc Natl Acad Sci USA 90: 755–759
Feldmeyer D, Kask K, Brusa R, Kornau HC, Kolhekar R, Rozov A, Burnashev N, Jensen V, Hvalby O, Sprengel R, Seeburg PH (1999) Neurological dysfunction in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B. Nat Neurosci 2: 57–64
Gerber AP, Keller W (2001) RNA editing by base deamination: more enzymes, more targets, new mysteries. Trends Biochem Sci 26: 376–384
Greger IH, Khatri L, Ziff EB (2002) RNA editing at arg607 controls AMPA receptor exit from the endoplasmic reticulum. Neuron 34: 759–772
Greger IH, Khatri L, Kong X, Ziff EB (2003) AMPA receptor tetramerization is mediated by Q/R editing. Neuron 40(4): 763–774
Grigorenko EV, Bell WL, Glazier S, Pons T, Deadwyler S (1998) Editing status at the Q/R site of the GluR2 and GluR6 glutamate receptor subunits in the surgically excised hippocampus of patients with refractory epilepsy. NeuroReport 9: 2219–2224
Higuchi M, Maas S, Single FN, Hartner J, Rozov A, Burnashev N, Feldmeyer D, Sprengel R, Seeburg PH (2000) Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 406: 78–81
Kamboj SK, Swanson GT, Cull-Candy SG (1995) Intracellular spermine confers rectification on rat calcium-permeable AMPA and Kainate receptors. J Physiol 486: 297–303
Kask K, Zamanillo D, Rozov A, Burnashev N, Sprengel R, Seeburg PH (1998) The AMPA receptor subunit GluR-B in its Q/R site-unedited form is not essential for brain development and function. Proc Natl Acad Sci USA 98: 13777–13782
Keegan PL, Gallo A, O’Connell MA (2001) The many roles of an RNA editor. Nat Rev Genet 2: 869–878
Kohler M, Burnashev N, Sakmann B, Seeburg PH (1993) Determination of Ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels; diversity by RNA editing. Neuron 10: 491–500
Kortenbruck G, Berger E, Speckmann EJ, Musshoff U (2001) RNA editing at the Q/R site for the glutamate receptor subunits GLUR2, GLUR5, and GLUR6 in hippocampus and temporal cortex from epileptic patients. Neurobiol Dis 8: 459–468
Krampfl K, Schlesinger F, Zorner A, Kappler M, Dengler R, Bufler J (2002) Control of kinetic properties of GluR2 flop AMPA-type channels: impact of R/G nuclear editing. Eur J Neurosci 15: 51–62
Lomeli H, Sprengel R, Laurie DJ, Kohr G, Herb A, Seeburg PH, Wisden W (1993) The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family. FEBS Lett 315: 318–322
Lomeli H, Mosbacher J, Melcher T, Hoger T, Geiger JR, Kuner T, Monyer H, Higuchi M, Bach A, Seeburg PH (1994) Control of kinetic properties of AMPA receptor channels by nuclear RNA editing. Science 266: 1709–1713
Niswender CM, Herrick-Davis K, Dilley GE, Meltzer HY, Overholser JC, Stockmeier CA, Emeson RB, Sanders-Bush E (2001) RNA editing of the human serotonin 5-HT2C receptor alterations in suicide and implications for serotonergic pharmacotherapy. Neuropsychopharmacology 24(5): 478–491
Powell LM, Wallis SC, Pease RJ, Edwards YH, Knott TJ, Scott J (1987) A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell 50: 831–840
Reenan RA (2001) The RNA world meets behavior: A-I pre-mRNA editing in animals. Trends Genet 17: 53–56
Sailer A, Swanson GT, Perez-Otano I, O’Leary L, Malkmus SA, Dyck RH, Dickinson-Anson H, Schiffer HH, Maron C, Yaksh TL, Gage FH, O’Gorman S, Heinemann SF (1999) Generation and analysis of GluR5(Q636R) kainate receptor mutant mice. J Neurosci 19(20): 8757–8764
Schmauss C (2003) Serotonin 2C receptors: suicide, serotonin, and runaway RNA editing. Neuroscientist 9(4): 237–242
Schmauss C, Howe JR (2002) RNA editing of neurotransmitter receptors in the mammalian brain. Sci STKE (133) PE26
Seeburg PH (2002) A-to-I editing: new and old sites, functions and speculations. Neuron 35(1): 17–20
Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of glutamate receptor channels: mechanism and physiology. Brain Res Rev 26: 217–229
Sodhi MS, Burnet PW, Makoff AJ, Kerwin RW, Harrison PJ (2001) RNA editing of the 5-HT(2C) receptor is reduced in schizophrenia. Mol Psychiatry 6(4): 373–379
Swanson GT, Feldmeyer D, Kaneda M, Cull-Candy SG (1996) Effect of RNA editing and subunit co-assembly single-channel properties of recombinant kainate receptors. J Physiol 492: 129–142
Vissel B, Royle GA, Christie BR, Schiffer HH, Ghetti A, Tritto T, Perez-Otano I, Radcliffe RA, Seamans J, Sejnowski T, Wehner JM, Collins AC, O’Gorman S, Heinemann SF (2001) The role of RNA editing of kainate receptors in synaptic plasticity and seizures. Neuron 29: 217–227
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Barlati, S., Barbon, A. (2005). RNA editing: a molecular mechanism for the fine modulation of neuronal transmission. In: von Wild, K.R.H. (eds) Re-Engineering of the Damaged Brain and Spinal Cord. Acta Neurochirurgica Supplementum, vol 93. Springer, Vienna. https://doi.org/10.1007/3-211-27577-0_7
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DOI: https://doi.org/10.1007/3-211-27577-0_7
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