RNA editing of AMPA receptor subunit GluR-B: A base-paired intron-exon structure determines position and efficiency

Higuchi, Miyoko; Single, Frank Nicolai; Köhler, Martin; Sommer, Bernd; Sprengel, Rolf; Seeburg, Peter H.

doi:10.1016/0092-8674(93)90622-w

Cited by 628 publications

(597 citation statements)

References 31 publications

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“…By contrast, shorts dsRNAs (∼20-30 bp) or a long but partially dsRNA with mismatched bases, bulges and loops (imperfect dsRNAs) are edited selectively; only a few adenosines are specifically chosen, indicating that the secondary structure in ADAR substrates dictates editing-site selectivity 48 . For example, site-selective A→I RNA editing occurs on an imperfect fold-back dsRNA structure that is formed between the exon sequence around an editing site(s) and a downstream intronic complementary sequence, termed editing-site-complementary sequence (ECS), of glutamate receptor-2 (GluR2) and serotonin (5-HT) receptor-2C (5-HT 2C R) pre-mRNAs 49,50 (see FIG. 3 and below).…”

Section: Substrate and Editing-site Selectivitymentioning

confidence: 99%

“…A limited number of targets (∼30 genes), such as mammalian GluR 49 and 5-HT 2C R 55 as well as potassium channel Kv1.1 ( REF. 56 ) and D. melanogaster Na + -channel 57 gene transcripts, have been identified that are subjected to A→I RNA editing in their coding sequences 51,52,56 .…”

Section: Physiological Significance Of Editing Editing Sites Found Inmentioning

confidence: 99%

“…a | L-glutamate is the predominant excitatory neurotransmitter in vertebrate nervous systems, and the glutamate receptor (GluR) has been implicated in neuronal plasticity and higher functions such as memory and learning 51 . Adenosine to inosine (A→I) RNA editing of the Gln/Arg (Q/R) site leads to the replacement of a Gln by an Arg residue 49,51 . Ion-channel receptors that contain the edited GluR2 subunit are impermeable to Ca 2+ , whereas channels that lack the edited subunit permit influx of Ca 2+ .…”

Section: Single Nucleotide Polymorphism (Snp)mentioning

confidence: 99%

“…3). Seeburg and colleagues identified a total of eight A→I RNA editing sites in the coding regions of receptors for several GluR subunits 49,51 . Among the eight editing sites, the Gln/Arg (Q/R) site located in the channel-pore-loop domain of the GluR2 subunit has the most important role in ionchannel function; editing of this single site makes the tetrameric channel protein impermeable to Ca 2+ (FIG.…”

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confidence: 99%

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Editor meets silencer: crosstalk between RNA editing and RNA interference

Nishikura

2006

Nat Rev Mol Cell Biol

257

263

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The most prevalent type of RNA editing is mediated by ADAR (adenosine deaminase acting on RNA) enzymes, which convert adenosines to inosines (a process known as A→I RNA editing) in double-stranded (ds)RNA substrates. A→I RNA editing was long thought to affect only selected transcripts by altering the proteins they encode. However, genome-wide screening has revealed numerous editing sites within inverted Alu repeats in introns and untranslated regions. Also, recent evidence indicates that A→I RNA editing crosstalks with RNA-interference pathways, which, like A→I RNA editing, involve dsRNAs. A→I RNA editing therefore seems to have additional functions, including the regulation of retrotransposons and gene silencing, which adds a new urgency to the challenges of fully understanding ADAR functions.An RNA transcript is subjected to various maturation processes, such as 5′ capping, splicing, 3′ processing and polyadenylation, after it is transcribed from the gene. Post-transcriptional processing of primary transcripts is essential to generate mature messenger RNAs that are ready to be translated into proteins 1 . RNA editing is a post-transcriptional-processing mechanism that results in an RNA sequence that is different from the one encoded by the genome, and thereby contributes to the diversity of gene products. There are different types of RNA-editing mechanism that either add or delete nucleotides, or that change one nucleotide into another 2 (BOX 1).The type of RNA editing that is most prevalent in higher eukaryotes converts adenosine (A) residues into inosine (I) in double-stranded (ds)RNAs through the action of ADAR (adenosine deaminase acting on RNA) enzymes [3][4][5] . A→I RNA editing of a short dsRNA that has formed between a coding exon and nearby intron sequences can lead to a codon change and an alteration in the protein function. However, it was recently discovered that the most frequent targets of A→I RNA editing seem to be long, but partially double-stranded, RNAs that are formed from inverted Alu repeats and long interspersed element (LINE) repeats located in introns and untranslated regions (UTRs) of mRNAs [6][7][8][9] . Global editing of non-coding RNA might control the expression of genes that harbour these repeat sequences of retrotransposon origin.Post-transcriptional gene regulation can also occur through RNA interference (RNAi), an evolutionarily conserved phenomenon that involves dsRNA molecules 10,11 . Small interfering RNAs (siRNAs) and microRNAs (miRNAs) are non-coding RNAs that are generated by a class of RNase III ribonucleases (specifically, Dicer and Drosha). These small RNAs are incorporated into the RNA-induced silencing complex (RISC), which mediates the RNAi process [12][13][14][15][16] . The idea that the RNAi and A→I RNA editing pathways might compete for a Competing interests statement: The author declares no competing financial interests. [23][24][25] . NIH Public AccessIn this review, I discuss recent findings on new functions of A→I RNA editing in the regulation of non...

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Section: Substrate and Editing-site Selectivitymentioning

confidence: 99%

Section: Physiological Significance Of Editing Editing Sites Found Inmentioning

confidence: 99%

Section: Single Nucleotide Polymorphism (Snp)mentioning

confidence: 99%

mentioning

confidence: 99%

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Editor meets silencer: crosstalk between RNA editing and RNA interference

Nishikura

2006

Nat Rev Mol Cell Biol

257

263

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“…16,17 A limited number of gene transcripts (B30), mostly those that encode channels and neurotransmitter receptors (for example, mammalian glutamate receptors, 5-HT 2C R, potassium channel Kv1.1, and Drosophila melanogaster sodium channel), have been identified to date. [18][19][20][21] When editing occurs within a coding region, it has the potential to alter codon specificity because the ribosome reads inosine as guanosine (G) resulting in altered amino-acid sequence and potentially protein function. In most cases, edited and unedited versions of a given receptor/channel coexist expanding the functional range of the receptor population.…”

Section: Introductionmentioning

confidence: 99%

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

et al. 2007

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Suicide is a major public health problem with B1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT 2C R) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT 2C R mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants (ACD and ABCD) that encode one of the most prevalent and highly edited isoforms of 5-HT 2C R, that is, VSV (Val156-Ser158-Val160). Because the VSV isoform of 5-HT 2C R exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior.

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