A distant cis acting intronic element induces site-selective RNA editing

Daniel, Chammiran; Ekdahl, Ylva; Kjems, Jørgen; Öhman, Marie

doi:10.1093/nar/gks691

Cited by 56 publications

(76 citation statements)

References 39 publications

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“…Traditional experimental manipulation of RNA-editing structures are usually conducted in vitro 28 or with mini-gene reporters in culture 29,30 . Many of these studies generally recapitulate editing and delineate important cis elements.…”

Section: Resultsmentioning

confidence: 99%

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Tertiary structural elements determine the extent and specificity of messenger RNA editing

et al. 2013

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The specificity and extent of RNA editing by ADAR enzymes is determined largely by local primary sequence and secondary structural imperfections in duplex RNA. Here we surgically alter conserved cis elements associated with a cluster of ADAR modification sites within the endogenous Drosophila paralytic transcript. In addition to the local requirement for a central imperfect RNA duplex containing the modified adenosines, we demonstrate that a secondary RNA duplex containing splicing signals strongly modulates RNA editing. A subtle non-coding mutation, extending base pairing of this accessory helix, confers significant phenotypic consequences via effects on splicing. Through mutation/counter-mutation, we also uncover and functionally replace a highly conserved intronic long-range tertiary pseudoknot that is absolutely required for deamination of one particular adenosine in the central duplex. Our results demonstrate that complex RNA tertiary structures, which may be difficult to predict computationally, form in vivo and can regulate RNA-editing events.

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Section: Resultsmentioning

confidence: 99%

“…An intronic duplex distant from splicing signals in the mammalian Gabra-3 transcript was recently reported to stimulate specific editing 28 . The authors hypothesized that the duplex serves to generically increase ADAR concentration locally, differing from our proposed mechanism.…”

Section: Nature Communications | Doimentioning

confidence: 99%

Tertiary structural elements determine the extent and specificity of messenger RNA editing

et al. 2013

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“…The RNA structures vary in size, but are often quite large, requiring a hundred or more base-pairing interactions. In most cases, they form between exonic and intronic sequences within pre-mRNAs, and sometimes these elements are separated by kilobases of intervening sequence (Daniel et al, 2012;Herb et al, 1996). The requirement for intronic sequence, and the fact that ADARs are confined to the nucleus, dictates that editing also occurs within the nucleus.…”

Section: Cephalopod Rna Editing Breaks the Rulesmentioning

confidence: 99%

The emerging role of RNA editing in plasticity

Rosenthal¹

2015

Journal of Experimental Biology

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All true metazoans modify their RNAs by converting specific adenosine residues to inosine. Because inosine binds to cytosine, it is a biological mimic for guanosine. This subtle change, termed RNA editing, can have diverse effects on various RNA-mediated cellular pathways, including RNA interference, innate immunity, retrotransposon defense and messenger RNA recoding. Because RNA editing can be regulated, it is an ideal tool for increasing genetic diversity, adaptation and environmental acclimation. This review will cover the following themes related to RNA editing: (1) how it is used to modify different cellular RNAs, (2) how frequently it is used by different organisms to recode mRNA, (3) how specific recoding events regulate protein function, (4) how it is used in adaptation and (5) emerging evidence that it can be used for acclimation. Organismal biologists with an interest in adaptation and acclimation, but with little knowledge of RNA editing, are the intended audience.

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“…NOD/ShiLtJ, which has higher editing than CAST/ EiJ, has a longer stretch of dsRNA in the full mRNA folded structure than CAST/EiJ ( Figure 5I). Recent reports have shown evidence of cis-acting intronic dsRNA elements that influence editing (Daniel et al 2012). We searched for promiscuous editing in the three genes shown in Figure 5 but did not find evidence of editing at sites other than the target editing sites.…”

Section: A-to-i Editingmentioning

confidence: 99%

Genetic Architectures of Quantitative Variation in RNA Editing Pathways

Gatti

Srivastava

et al. 2015

Genetics

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RNA editing refers to post-transcriptional processes that alter the base sequence of RNA. Recently, hundreds of new RNA editing targets have been reported. However, the mechanisms that determine the specificity and degree of editing are not well understood. We examined quantitative variation of site-specific editing in a genetically diverse multiparent population, Diversity Outbred mice, and mapped polymorphic loci that alter editing ratios globally for C-to-U editing and at specific sites for A-to-I editing. An allelic series in the C-to-U editing enzyme Apobec1 influences the editing efficiency of Apob and 58 additional C-to-U editing targets. We identified 49 A-to-I editing sites with polymorphisms in the edited transcript that alter editing efficiency. In contrast to the shared genetic control of C-to-U editing, most of the variable A-to-I editing sites were determined by local nucleotide polymorphisms in proximity to the editing site in the RNA secondary structure. Our results indicate that RNA editing is a quantitative trait subject to genetic variation and that evolutionary constraints have given rise to distinct genetic architectures in the two canonical types of RNA editing.KEYWORDS genetics; RNA editing; Diversity Outbred; Apobec1; secondary structure; Multiparent Advanced Generation Inter-Cross (MAGIC); multiparental populations; MPP R NA EDITING in mammals occurs through deamination of adenosine, which is converted to inosine (A-to-I editing), or deamination of cytosine, which is converted to uracil (C-to-U editing) (Davidson and Shelness 2000;Bass 2002). Other types of editing have been reported, but these findings remain controversial (Bass et al. 2012;Gu et al. 2012). The two canonical editing types, A-to-I and C-to-U editing, are mediated by distinct pathways. A-to-I editing is catalyzed on double-stranded (ds) RNA by proteins in the adenosine deaminase, RNA-specific (ADAR) family (ADAR1 and ADAR2) and is most common in neuronal tissues. However, the Adar gene family is ubiquitously expressed, and editing has been reported in many other tissues (Gu et al. 2012).Homozygous deletion of Adar genes is embryonic lethal in mice, and defects in A-to-I editing have been associated with neurodegenerative disorders and cancers (Gurevich et al. 2002;Paz et al. 2007). The C-to-U editing pathway is catalyzed by apolipoprotein B messenger RNA (mRNA) editing enzyme catalytic polypeptide 1 (Apobec1), which is expressed primarily in small intestine and liver, where it targets the transcript of apolipoprotein B (Apob), converting a CAA (glutamine) codon within the coding sequence to a stop codon (UAA). This editing event results in two APOB protein isoforms, APOB48 from the edited transcript and APOB100 from the unedited transcript. Editing of Apob is evolutionarily conserved and occurs in mice, humans, and other mammals. The edited isoform APOB48 functions in the synthesis, assembly, and secretion of chylomicrons in the small intestine; the unedited isoform APOB100 is expressed in the liver and gives ris...

show abstract

A distant cis acting intronic element induces site-selective RNA editing

Cited by 56 publications

References 39 publications

Tertiary structural elements determine the extent and specificity of messenger RNA editing

Tertiary structural elements determine the extent and specificity of messenger RNA editing

The emerging role of RNA editing in plasticity

Genetic Architectures of Quantitative Variation in RNA Editing Pathways

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