Developmental changes in expression and self-editing of adenosine deaminase type 2 pre-mRNA and mRNA in rat brain and cultured cortical neurons

Hang, Pham Nguyet Thi; Tohda, Michihisa; Matsumoto, Kinzo

doi:10.1016/j.neures.2008.04.007

Cited by 18 publications

(18 citation statements)

References 29 publications

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“…S2C). Previous studies have not been able to correlate ADAR expression levels to editing efficiency, 17,32,33 but also lack the same resolution in the overall data set.…”

mentioning

confidence: 94%

Spatio-temporal regulation of ADAR editing during development in porcine neural tissues

Bramsen

Berthou²,

Panitz³

et al. 2012

RNA Biology

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“…S2C). Previous studies have not been able to correlate ADAR expression levels to editing efficiency, 17,32,33 but also lack the same resolution in the overall data set.…”

mentioning

confidence: 94%

Spatio-temporal regulation of ADAR editing during development in porcine neural tissues

Bramsen

Berthou²,

Panitz³

et al. 2012

RNA Biology

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“…6,7) These results suggested that 5-HT2CR mRNA editing and these enzymes play a role in the brain's maturation. To find a pharmacological tool with which to investigate the roles of 5-HT2CR mRNA editing, we examined the effect of erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA), a well-known inhibitor of adenosine deaminase (ADA) which breaks extracellular adenosine, 8) on the editing of 5-HT2CR mRNA at sites A-D in cultured cortical cells.…”

mentioning

confidence: 82%

“…Cultured cortical cells prepared from E20 embryos as described previously 6,7) were used for the experiments. The cells were exposed to vehicle (control) or EHNA included in culture media at concentrations of 30 and 60 mM for 6 d.…”

Section: Methodsmentioning

confidence: 99%

“…6,7) The specific primers for target genes to identify the bases at editing sites were: 5-HT2CR mRNA (NM_008312); 5Ј-atg tcc cta gcc att gct gat atg ctg gtg-3Ј (sense), 5Ј-atg cca cga agg acc cga tga gaa cga agt-3Ј (antisense), and Texas Red-labeled: 5Ј-ata ttt gtg ccc cgt cgt ga; ADAR-2 pre-mRNA (NW_047598), 5Ј-atg tgc tgg tga act cac ag-3Ј (sense), 5Ј-gtg gtg ccc aga aag agt gg-3Ј (antisense) and Texas Red-labeled: 5Ј-taa gta gga gag gca ata ggt ccg-3Ј; and GluR2 (NM_017261), 5Ј-tat atg agg agt gca gag cc-3Ј (sense), 5Ј-ata ctc cag caa cgt tgc tc-3Ј (antisense) and Texas Red-labeled: 5Ј-ctg tgt ttg tga gga cta cc-3Ј. Based on pilot studies where we ran specific primers for target genes, the proper cycle number for the amplification of each target gene was chosen (5-HT2CR mRNA including the editing sites: 35; ADAR-2 pre-mRNA: 28 cycles; GluR2: 32 cycles).…”

Section: Methodsmentioning

confidence: 99%

“…To analyze the editing frequencies at sites A-D of 5-HT2CR mRNA, a direct sequencing method with a Tex-Red-labeled primer adapted to the PCR product was employed as previously reported. 6,7) All data were expressed as the meanϮS.E.M. and analyzed by a one-way analysis of variance (ANOVA) followed by the Student-Newman-Keuls test.…”

mentioning

confidence: 99%

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Influence of an Adenosine Deaminase Inhibitor, Erythro-9-(2-hydroxy-3-nonyl) Adenine Hydrochloride, on 5-HT2CR mRNA Editing in Primary Cultured Cortical Cells

Hang

Tohda

Tezuka

et al. 2010

Biological & Pharmaceutical Bulletin

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The adenosine to inosine RNA editing process mediated by adenosine deaminase acting on RNA (ADARs) has been reported to play critical roles in the functional development of the central nervous system by modulating the functions of neurotransmitter receptors. Serotonin 2C receptor (5-HT2CR) mRNA undergoes editing by these ADARs at 5 nucleotide positions (sites A-E) located in the sequence encoding the second intracellular loop of 5-HT2CR. This editing allows for the generation of 32 mRNA variants and 24 protein isoforms of the receptor differing in G-protein coupling efficiency.1) The involvement of 5-HT2CR mRNA editing in psychiatric disorders has been hypothesized based on etiological and pharmacological studies. Altered editing of 5-HT2CR mRNA was detected in the postmortem brains of patients with major depression, schizophrenia and bipolar disorder.2-4) Yang et al. 5) found that 5-HT2CR mRNA editing frequency in human glioblastoma cell lines was altered by treatment with interferon which causes depression as an adverse effect. These findings also raised the possibility that compounds with the ability to inhibit/stimulate the editing of 5-HT2CR mRNA are useful for clarifying the role of 5-HT2CR mRNA editing in psychiatric disorders.Our previous studies have shown that the editing efficacy of 5-HT2CR mRNA and ADAR-2 pre-mRNA and the level of ADAR-2 pre-mRNA are altered during the development of the brain in rats.6,7) These results suggested that 5-HT2CR mRNA editing and these enzymes play a role in the brain's maturation. To find a pharmacological tool with which to investigate the roles of 5-HT2CR mRNA editing, we examined the effect of erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA), a well-known inhibitor of adenosine deaminase (ADA) which breaks extracellular adenosine, 8) on the editing of 5-HT2CR mRNA at sites A-D in cultured cortical cells. MATERIALS AND METHODSCultured cortical cells prepared from E20 embryos as described previously 6,7) were used for the experiments. The cells were exposed to vehicle (control) or EHNA included in culture media at concentrations of 30 and 60 mM for 6 d.After a 6-d cultivation period, total RNA was extracted, and RT-PCR was carried out as described previously.6,7) The specific primers for target genes to identify the bases at editing sites were: 5-HT2CR mRNA (NM_008312); 5Ј-atg tcc cta gcc att gct gat atg ctg gtg-3Ј (sense), 5Ј-atg cca cga agg acc cga tga gaa cga agt-3Ј (antisense), and Texas Red-labeled: 5Ј-ata ttt gtg ccc cgt cgt ga; ADAR-2 pre-mRNA (NW_047598), 5Ј-atg tgc tgg tga act cac ag-3Ј (sense), 5Ј-gtg gtg ccc aga aag agt gg-3Ј (antisense) and Texas Red-labeled: 5Ј-taa gta gga gag gca ata ggt ccg-3Ј; and GluR2 (NM_017261), 5Ј-tat atg agg agt gca gag cc-3Ј (sense), 5Ј-ata ctc cag caa cgt tgc tc-3Ј (antisense) and Texas Red-labeled: 5Ј-ctg tgt ttg tga gga cta cc-3Ј. Based on pilot studies where we ran specific primers for target genes, the proper cycle number for the amplification of each target gene was chosen (5-HT2CR mRNA including the editing sit...

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Activity Regulation of Adenosine Deaminases Acting on RNA (ADARs)

2011

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Adenosine deaminases acting on RNA (ADARs) are the enzymes that are responsible for the A to I RNA editing process in mammals, which is an important mechanism that increases molecular diversity. A to I RNA editing consists of an enzymatic conversion of specific adenosine in pre-mRNA, leading to alteration of the properties of both the RNA itself and the translated protein. Currently, the importance of this phenomenon is increasingly recognized as it affects a diverse set of cellular pathways. ADAR function within the cell, especially in the neurons, is to diversify the features of a limited set of unique transcripts, mostly neurotransmitter receptors; however, a growing set of target is going to be discovered, increasing the importance of the RNA editing event in the proper physiology of the cell. Despite the functional relevance of these enzymes, there is a gap of knowledge in the mechanisms that regulate ADAR activity and consequently about the modulation of RNA editing process. This review summarizes ongoing investigations of ADAR regulation at the transcriptional, post-transcriptional and post-translational level and addresses new hypothetical mechanisms that are capable of modulating ADAR activity, including subcellular localization, dimerization and interaction with trans-acting factors.

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Developmental changes in expression and self-editing of adenosine deaminase type 2 pre-mRNA and mRNA in rat brain and cultured cortical neurons

Cited by 18 publications

References 29 publications

Spatio-temporal regulation of ADAR editing during development in porcine neural tissues

Spatio-temporal regulation of ADAR editing during development in porcine neural tissues

Influence of an Adenosine Deaminase Inhibitor, Erythro-9-(2-hydroxy-3-nonyl) Adenine Hydrochloride, on 5-HT2CR mRNA Editing in Primary Cultured Cortical Cells

Activity Regulation of Adenosine Deaminases Acting on RNA (ADARs)

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