RNA editing by ADARs is important for normal behavior in Caenorhabditis elegans

Tonkin, Leath A.; Saccomanno, Lisa; Morse, Daniel P.; Brodigan, Thomas M.; Krause, Michael; Bass, Brenda

doi:10.1093/emboj/cdf607

Cited by 205 publications

(266 citation statements)

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“…Drosophila melanogaster have only a single ADAR2-like gene, Adar 36 , whereas C. elegans have two ADAR genes, adar-1 and adar-2 ( REF. 24 ) (FIG. 2a).…”

Section: Adar Genesmentioning

confidence: 99%

“…Flies with a homozygous deletion in the Adar gene exhibit brain-related changes such as a lack of coordinated locomotion and age-dependent neurodegeneration 36 . Strains of C. elegans that contain homozygous deletions of both adar-1 and adar-2 display defective chemotaxis 24 . Mice with a homozygous Adar2-null mutation die several weeks after birth.…”

Section: Rna-editing Deficienciesmentioning

confidence: 99%

“…2a) display defective chemotaxis 24 . These phenotypic alterations, however, can be reverted in C. elegans strains that have an RNAi deficiency, indicating that ADAR-null worm phenotypes are RNAi dependent 23 .…”

Section: Suppression Of Rnai By A→i Rna Editingmentioning

confidence: 99%

“…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] . …”

mentioning

confidence: 99%

“…Furthermore, one of the mammalian ADAR-family members sequesters siRNAs, thereby reducing RNAi efficacy 22 . Last, analysis of ADAR-null Caenorhabditis elegans strains indicates that A→I RNA editing might counteract RNAi silencing of endogenous genes and transgenes [23][24][25] .…”

mentioning

confidence: 99%

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Editor meets silencer: crosstalk between RNA editing and RNA interference

Nishikura

2006

Nat Rev Mol Cell Biol

258

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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“…Drosophila melanogaster have only a single ADAR2-like gene, Adar 36 , whereas C. elegans have two ADAR genes, adar-1 and adar-2 ( REF. 24 ) (FIG. 2a).…”

Section: Adar Genesmentioning

confidence: 99%

Section: Rna-editing Deficienciesmentioning

confidence: 99%

Section: Suppression Of Rnai By A→i Rna Editingmentioning

confidence: 99%

“…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] . …”

mentioning

confidence: 99%

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confidence: 99%

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