Proteome diversification by adenosine to inosine RNA-editing

Pullirsch, Dieter; Jantsch, Michael F.

doi:10.4161/rna.7.2.11286

Cited by 65 publications

(61 citation statements)

References 76 publications

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“…Consistent with these observations, A to I editing is required for nervous system function in metazoans (9-11). However, although both of the enzymes responsible for A to I editing in humans (ADAR1 and ADAR2) are expressed in tissues throughout the body, little is known about the effect of recoding of targets with roles outside the nervous system (7).…”

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confidence: 99%

“…Current estimates have the number of A to I sites in the human transcriptome at >15;000 with the vast majority of these sites occurring in Alu repeats (5). However, hundreds of A to I sites also occur in nonrepeat sequences with at least 50 different recoding events known in human cells (6,7). Recoding by adenosine deamination is common in the nervous system with targets including ligand-gated ion channels, voltage-gated ion channels, and G-protein coupled receptors (2,3,8).…”

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confidence: 99%

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RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1

Yeo

Goodman

Schirle

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

137

194

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Editing of the pre-mRNA for the DNA repair enzyme NEIL1 causes a lysine to arginine change in the lesion recognition loop of the protein. The two forms of NEIL1 are shown here to have distinct enzymatic properties. The edited form removes thymine glycol from duplex DNA 30 times more slowly than the form encoded in the genome, whereas editing enhances repair of the guanidinohydantoin lesion by NEIL1. In addition, we show that the NEIL1 recoding site is a preferred editing site for the RNA editing adenosine deaminase ADAR1. The edited adenosine resides in an A-C mismatch in a hairpin stem formed by pairing of exon 6 to the immediate upstream intron 5 sequence. As expected for an ADAR1 site, editing at this position is increased in human cells treated with interferon α. These results suggest a unique regulatory mechanism for DNA repair and extend our understanding of the impact of RNA editing.ADAR | nucleic acids | base excision repair | oxidative stress | DNA damage

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confidence: 99%

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confidence: 99%

RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1

Yeo

Goodman

Schirle

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

137

194

View full text Add to dashboard Cite

show abstract

“…On the basis of its overabundance in repetitive Alu elements and the brain transcriptome [1][2][3] , RNA editing has been viewed as a key determinant in primate evolution and the development of higher brain functions 4 . Many outstanding questions on the extent and consequences of RNA editing in humans remain unanswered, despite extensive documentation of edited sites through bioinformatics approaches [5][6][7][8][9] and the reported roles of editing in altering genetic messages and other post-transcriptional events such as RNA splicing and miRNA regulation 2,[10][11][12] . Global and unequivocal identification of RNA editing targets represents a critical first step in further understanding this post-transcriptional modification.…”

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confidence: 99%

Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome

et al. 2012

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A n A ly s i s RNA editing is a post-transcriptional event that recodes hereditary information. Here we describe a comprehensive profile of the RNA editome of a male Han Chinese individual based on analysis of ~767 million sequencing reads from poly(A) + , poly(A) − and small RNA samples. We developed a computational pipeline that carefully controls for false positives while calling RNA editing events from genome and whole-transcriptome data of the same individual. We identified 22,688 RNA editing events in noncoding genes and introns, untranslated regions and coding sequences of protein-coding genes. Most changes (~93%) converted A to I(G), consistent with known editing mechanisms based on adenosine deaminase acting on RNA (ADAR). We also found evidence of other types of nucleotide changes; however, these were validated at lower rates. We found 44 editing sites in microRNAs (miRNAs), suggesting a potential link between RNA editing and miRNAmediated regulation. Our approach facilitates large-scale studies to profile and compare editomes across a wide range of samples.RNA editing is an integral step in generating the diversity and plasticity of cellular RNA signatures. Most editing events convert A to I(G) (adenosine to inosine, which is translated as guanosine), and are catalyzed by the double-stranded RNA-specific ADAR family of proteins. On the basis of its overabundance in repetitive Alu elements and the brain transcriptome 1-3 , RNA editing has been viewed as a key determinant in primate evolution and the development of higher brain functions 4 . Many outstanding questions on the extent and consequences of RNA editing in humans remain unanswered, despite extensive documentation of edited sites through bioinformatics approaches 5-9 and the reported roles of editing in altering genetic messages and other post-transcriptional events such as RNA splicing and miRNA regulation 2,10-12 . Global and unequivocal identification of RNA editing targets represents a critical first step in further understanding this post-transcriptional modification. This calls for complete information on whole-genome and transcriptome sequences from the same individual, so as to exclude polymorphisms and mutations among populations, as well as experimental approaches with the necessary high-throughput sequencing and base resolution 13,14 . Whole-transcriptome deep-sequencing technologies (e.g., RNASeq) [15][16][17] , with their capacity to simultaneously assay the entire transcriptome, represent an excellent choice of tool in this regard. Recent studies reporting the use of target-specific RNA-Seq 4,18 , the combination of DNA capture and parallel sequencing 19 , and mRNA-Seq 20,21 to find human RNA editing sites attest to the notion that this strategy is advantageous in addressing many outstanding questions of the editing phenomenon and its implications on the transcriptome.In this study, we used RNA-Seq to identify post-transcriptional editing events. Our unbiased and in-depth approach revealed many editing sites in transcripts corresp...

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“…In particular, base-modification editing of adenosine (A) to inosine (I) within pre-mRNA was shown to be a widespread form of information recording of mRNA codons in higher eukaryotes (Nishikura 2010;Pullirsch and Jantsch 2010). A-to-I substitutions in protein-coding sequences may result in codon changes because inosine is decoded as guanosine by the ribosome during translation.…”

Section: Introductionmentioning

confidence: 99%

A strategy for developing a hammerhead ribozyme for selective RNA cleavage depending on substitutional RNA editing

Fukuda¹,

Kurihara²,

Tanaka³

et al. 2012

RNA

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Substitutional RNA editing plays a crucial role in the regulation of biological processes. Cleavage of target RNA that depends on the specific site of substitutional RNA editing is a useful tool for analyzing and regulating intracellular processes related to RNA editing. Hammerhead ribozymes have been utilized as small catalytic RNAs for cleaving target RNA at a specific site and may be used for RNA-editing-specific RNA cleavage. Here we reveal a design strategy for a hammerhead ribozyme that specifically recognizes adenosine to inosine (A-to-I) and cytosine to uracil (C-to-U) substitutional RNA-editing sites and cleaves target RNA. Because the hammerhead ribozyme cleaves one base upstream of the target-editing site, the base that pairs with the targetediting site was utilized for recognition. RNA-editing-specific ribozymes were designed such that the recognition base paired only with the edited base. These ribozymes showed A-to-I and C-to-U editing-specific cleavage activity against synthetic serotonin receptor 2C and apolipoprotein B mRNA fragments in vitro, respectively. Additionally, the ribozyme designed for recognizing A-to-I RNA editing at the Q/R site on filamin A (FLNA) showed editing-specific cleavage activity against physiologically edited FLNA mRNA extracted from cells. We demonstrated that our strategy is effective for cleaving target RNA in an editing-dependent manner. The data in this study provided an experimental basis for the RNA-editing-dependent degradation of specific target RNA in vivo.

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Proteome diversification by adenosine to inosine RNA-editing

Cited by 65 publications

References 76 publications

RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1

RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1

Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome

A strategy for developing a hammerhead ribozyme for selective RNA cleavage depending on substitutional RNA editing

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