Extensive adenosine‐to‐inosine editing detected in <i>Alu</i> repeats of antisense RNAs reveals scarcity of sense–antisense duplex formation

Kawahara, Yukio; Nishikura, Kazuko

doi:10.1016/j.febslet.2006.03.042

Cited by 37 publications

(42 citation statements)

References 24 publications

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“…However, A→I RNA editing is not detected in the regions outside of repetitive sequences 75 . PCR after reverse transcription of RNA (RT-PCR) and sequencing analysis of sense and antisense cyclin CNNM3 RNAs derived from an intronic region that contains two inverted Alu repeats confirmed that both sense and antisense RNAs are extensively edited, but only in their intramolecular fold-back dsRNA structures 76 (FIG. 4b).…”

Section: Editing Of Non-coding Antisense Transcriptsmentioning

confidence: 94%

“…4b). No editing was detected outside of the Alu sequences, which indicates that the formation of an intermolecular sense-antisense RNA duplex does not occur 76 (FIG. 4c).…”

Section: Editing Of Non-coding Antisense Transcriptsmentioning

confidence: 96%

“…4c). Interestingly, analysis of an equimolar mixture of sense and antisense CNNM3 RNAs that were edited in vitro by recombinant ADAR1 and ADAR2 indicate again that A→I RNA editing is restricted to the intramolecular fold-back structure, which indicates that inversely oriented Alu repeats predominantly form an intramolecular dsRNA and that their interaction with ADARs might prevent the formation of intermolecular RNA duplexes 76 .…”

Section: Editing Of Non-coding Antisense Transcriptsmentioning

confidence: 99%

“…Several intronic editing sites that have been detected in GluR2 and 5-HT 2C R dsRNAs are not shown. while analysing RT-PCR products 76 . As with CNNM3 pre-mRNA, extensive A→I RNA editing of these antisense transcripts was limited to the Alu-repeat sequences (shown in red and green), which indicated that sense and antisense strand RNAs formed two separate intramolecular dsRNAs instead of a completely complementary, long intermolecular dsRNA 76 .…”

Section: Single Nucleotide Polymorphism (Snp)mentioning

confidence: 99%

“…while analysing RT-PCR products 76 . As with CNNM3 pre-mRNA, extensive A→I RNA editing of these antisense transcripts was limited to the Alu-repeat sequences (shown in red and green), which indicated that sense and antisense strand RNAs formed two separate intramolecular dsRNAs instead of a completely complementary, long intermolecular dsRNA 76 . Together, it seems that in vivo formation of intermolecular RNA duplexes of sense and antisense transcripts is very rare, if it occurs at all.…”

Section: Single Nucleotide Polymorphism (Snp)mentioning

confidence: 99%

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Editor meets silencer: crosstalk between RNA editing and RNA interference

Nishikura

2006

Nat Rev Mol Cell Biol

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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: Editing Of Non-coding Antisense Transcriptsmentioning

confidence: 94%

“…4b). No editing was detected outside of the Alu sequences, which indicates that the formation of an intermolecular sense-antisense RNA duplex does not occur 76 (FIG. 4c).…”

Section: Editing Of Non-coding Antisense Transcriptsmentioning

confidence: 96%

Section: Editing Of Non-coding Antisense Transcriptsmentioning

confidence: 99%

Section: Single Nucleotide Polymorphism (Snp)mentioning

confidence: 99%

Section: Single Nucleotide Polymorphism (Snp)mentioning

confidence: 99%

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Editor meets silencer: crosstalk between RNA editing and RNA interference

Nishikura

2006

Nat Rev Mol Cell Biol

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257

263

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Posttranscriptional Gene Regulation by an Editor: ADAR and its Role in RNA Editing

Valente

Kawahara

Zinshteyn

et al. 2013

Posttranscriptional Gene Regulation

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Epigenetics and the nervous system

Mehler

2008

Annals of Neurology

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We are in the midst of a revolution in the genomic sciences that will forever change the way we view biology and medicine, particularly with respect to brain form, function, development, evolution, plasticity, neurological disease pathogenesis and neural regenerative potential. The application of epigenetic principles has already begun to identify and characterize previously unrecognized molecular signatures of disease latency, onset and progression, mechanisms underlying disease pathogenesis, and responses to new and evolving therapeutic modalities. Moreover, epigenomic medicine promises to usher in a new era of neurological therapeutics designed to promote disease prevention and recovery of seemingly lost neurological function via reprogramming of stem cells, redirecting cell fate decisions and dynamically modulating neural network plasticity and connectivity.

show abstract

Extensive adenosine‐to‐inosine editing detected in Alu repeats of antisense RNAs reveals scarcity of sense–antisense duplex formation

Cited by 37 publications

References 24 publications

Editor meets silencer: crosstalk between RNA editing and RNA interference

Editor meets silencer: crosstalk between RNA editing and RNA interference

Posttranscriptional Gene Regulation by an Editor: ADAR and its Role in RNA Editing

Epigenetics and the nervous system

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