Regional analysis of developmental changes in the extent of GluR6 mRNA editing in rat brain

Schmitt, Justina; Dux, E.; Gissel, Cornelia; Paschen, Wulf

doi:10.1016/0165-3806(95)00175-1

Cited by 28 publications

(20 citation statements)

References 20 publications

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“…We find this site to be edited in all except one transcript already at E15. However, it has previously been shown in rat that the equivalent Q/R site in Grik1 and Grik2 is developmentally regulated (Bernard and Khrestchatisky 1994;Paschen et al 1994;Schmitt et al 1996). Our data are in total agreement with these analyses, but in addition, we can see that the I/V and Y/C sites of Grik2 also are edited with a low efficiency at embryogenesis that increases during development.…”

Section: Discussionsupporting

confidence: 82%

“…Auto-editing at this position has been proposed to be a mechanism for ADARB1 to balance its own expression (Feng et al 2006). Previous studies show that editing of some sites in the kainate and the AMPA glutamate receptor transcripts in rat are regulated during development (Lomeli et al 1994;Paschen et al 1994;Schmitt et al 1996;Bernard et al 1999). Owing to the large impact of A-to-I editing on several processes in the CNS, it is of interest to understand how editing is regulated and what impact an altered editing activity may have on the developing brain.…”

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confidence: 99%

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Large-scale mRNA sequencing determines global regulation of RNA editing during brain development

Wahlstedt¹,

Daniel²,

Ensterö³

et al. 2009

Genome Res.

276

304

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RNA editing by adenosine deamination has been shown to generate multiple isoforms of several neural receptors, often with profound effects on receptor function. However, little is known about the regulation of editing activity during development. We have developed a large-scale RNA sequencing protocol to determine adenosine-to-inosine (A-to-I) editing frequencies in the coding region of genes in the mammalian brain. Using the 454 Life Sciences (Roche) Amplicon Sequencing technology, we were able to determine even low levels of editing with high accuracy. The efficiency of editing for 28 different sites was analyzed during the development of the mouse brain from embryogenesis to adulthood. We show that, with few exceptions, the editing efficiency is low during embryogenesis, increasing gradually at different rates up to the adult mouse. The variation in editing gave receptors like HTR2C and GABA A (gamma-aminobutyric acid type A) a different set of protein isoforms during development from those in the adult animal. Furthermore, we show that this regulation of editing activity cannot be explained by an altered expression of the ADAR proteins but, rather, by the presence of a regulatory network that controls the editing activity during development.

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 99%

Large-scale mRNA sequencing determines global regulation of RNA editing during brain development

Wahlstedt¹,

Daniel²,

Ensterö³

et al. 2009

Genome Res.

276

304

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show abstract

“…53 The extent of GluK2 editing of the Q/R site that we observed in the cerebral tissue of control animals (84%) was consistent with previously reported values of 80%-90% in rodent brains. 51,[55][56][57] The tendency toward slightly greater editing at the Q/R site than at the 2 other sites confirms the previous results of Barbon and colleagues. 51 The editing in the cultured astrocytes was much more extensive than previously reported, [57][58][59] perhaps reflecting the differentiation induced by dBcAMP.…”

Section: Discussionsupporting

confidence: 81%

Fluoxetine affects GluK2 editing, glutamate-evoked Ca²⁺ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Zhang

et al. 2011

jpn

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. Background:We sought to study the effects of chronic exposure to fluoxetine -a selective serotonin reuptake inhibitor (SSRI) and specific 5-HT 2B receptor agonist in astrocytes -on the expression of kainate receptors (GluK1-5) in cultured astrocytes and in intact brains in mice and on GluK2 editing by adenosine deaminase acting on RNA (ADAR), as well as the ensuing effects of fluoxetine on glutamate-mediated Ca 2+ influx and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in astrocytes. Methods: We performed reverse transcription-polymerase chain reaction (PCR) to assess mRNA expression. We analyzed RNA editing with amplification refractory mutation system PCR and complementary DNA sequencing. Protein expression and ERK phosphorylation were assessed using Western blots. We studied gene silencing with specific small interfering RNAs (siRNA), and we studied intracellular Ca 2+ using fluorometry. Results: All GluK subunits were present in the brain in vivo, and GluK2-5 subunits were present in cultured astrocytes. Fluoxetine upregulated GluK2 and ADAR2. Enhanced GluK2 editing by fluoxetine abolished glutamate-mediated increases in intra cellular Ca 2+ and ERK 1/2 phosphorylation. Enhanced editing of GluK2 was prevented by siRNA against the 5-HT 2B receptor or ADAR2. Limitations: Limitations of our study include the use of an in vitro system, but our cultured cells in many respects behave like in vivo astrocytes. Conclusion: Fluoxetine alters astrocytic glutamatergic function.

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“…For instance, very little Q/R site editing of GluR5 and GluR6 occurs during early embryonic life, with a significant increase in the proportion of editing by adulthood (Bernard and Khrestchatisky, 1994;Paschen et al, 1994Paschen et al, , 1995Schmitt et al, 1996). A dramatic increase in the editing efficiency for the R/G site of GIuR-B, C, and D subunits during development has also been reported (Lomeli et a!., 1994).…”

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confidence: 90%

Dramatic Increase of the RNA Editing for Glutamate Receptor Subunits During Terminal Differentiation of Clonal Human Neurons

Lai

Chen

Lee

et al. 1997

Journal of Neurochemistry

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RNA editing plays an important role in determining physiological characteristics of certain glutamate-gated receptor (GIuR) channels such as Ca 2 permeability and desensitization kinetics. In one case, the editing changes a gene-encoded glutamine (0) to an arginine (R) codon located in the channel-forming domain of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunit GIuR-B and also the kainate receptor subunits GIuR5 and GIuR6. Another case of RNA editing alters an arginine (R) to a glycine (G) codon at a position termed the "RIG" site of AMPA subunits GIuR-B, C, and D. Double-stranded RNA-specific adenosine deaminases (DRADA) have been implicated as agents involved in the editing. By using a human teratocarcinoma cell line, NT2, we investigated the change of the RNA editing of GIuR subunits in conjunction with the expression of two DRADA members, DRADA1 and DRADA2 genes, during neuronal differentiation. Whereas OIR and R/G site RNA editing both become progressively activated in differentiating NT2 cells, the expression of the two DRADA genes can already be detected even in the undifferentiated NT2 cells. Developmentof the editing machinery appears to require, in addition to DRADA enzymes, a currently unidentified mechanism(s) that may become activated during neuronal differentiation. Key Words: Double-stranded RNA-dsRNA adenosine deaminase-dsRNA binding protein-Glutamate receptor channel-RNA editing.

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Regional analysis of developmental changes in the extent of GluR6 mRNA editing in rat brain

Cited by 28 publications

References 20 publications

Large-scale mRNA sequencing determines global regulation of RNA editing during brain development

Large-scale mRNA sequencing determines global regulation of RNA editing during brain development

Fluoxetine affects GluK2 editing, glutamate-evoked Ca²⁺ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Dramatic Increase of the RNA Editing for Glutamate Receptor Subunits During Terminal Differentiation of Clonal Human Neurons

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Regional analysis of developmental changes in the extent of GluR6 mRNA editing in rat brain

Cited by 28 publications

References 20 publications

Large-scale mRNA sequencing determines global regulation of RNA editing during brain development

Large-scale mRNA sequencing determines global regulation of RNA editing during brain development

Fluoxetine affects GluK2 editing, glutamate-evoked Ca2+ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes

Dramatic Increase of the RNA Editing for Glutamate Receptor Subunits During Terminal Differentiation of Clonal Human Neurons

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Fluoxetine affects GluK2 editing, glutamate-evoked Ca²⁺ influx and extracellular signal-regulated kinase phosphorylation in mouse astrocytes