ADAR Regulates RNA Editing, Transcript Stability, and Gene Expression

Wang, Isabel X.; So, Elizabeth; Devlin, James L.; Zhao, Yue; Wu, Ming‐Chi; Cheung, Vivian G.

doi:10.1016/j.celrep.2013.10.002

Cited by 180 publications

(209 citation statements)

References 53 publications

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“…As one might predict, editing has been shown to influence splicing (Agrawal and Stormo, 2005;Bratt and Ohman, 2003;Jin et al, 2007;Laurencikiene et al, 2006;Lev-Maor et al, 2008;Rueter et al, 1999;Ryman et al, 2007;Solomon et al, 2013) and mRNA stability (Chen and Carmichael, 2012;DeCerbo and Carmichael, 2005;Wang et al, 2013). It is reasonable to assume, therefore, that editing affects most RNA processing pathways.…”

Section: Adars Do Much More Than Alter Codonsmentioning

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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Section: Adars Do Much More Than Alter Codonsmentioning

confidence: 99%

The emerging role of RNA editing in plasticity

Rosenthal¹

2015

Journal of Experimental Biology

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“…In this study we sought to examine whether the editing of target mRNA, rather than miRNA, might affect mRNA:miRNA binding by altering seed matches. The possibility that miRNA target sites can be created or deleted by RNA editing has been proposed (23,28), but studies supporting this hypothesis are very limited (29,30).…”

Section: Discussionmentioning

confidence: 99%

RNA Editing Modulates Human Hepatic Aryl Hydrocarbon Receptor Expression by Creating MicroRNA Recognition Sequence

Nakano

Fukami

Gotoh

et al. 2016

Journal of Biological Chemistry

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Adenosine to inosine (A-to-I) RNA editing is the most frequent type of post-transcriptional nucleotide conversion in humans, and it is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes. In this study we investigated the effect of RNA editing on human aryl hydrocarbon receptor (AhR) expression because the AhR transcript potentially forms double-stranded structures, which are targets of ADAR enzymes. In human hepatocellular carcinoma-derived Huh-7 cells, the ADAR1 knockdown reduced the RNA editing levels in the 3-untranslated region (3-UTR) of the AhR transcript and increased the AhR protein levels. The ADAR1 knockdown enhanced the ligand-mediated induction of CYP1A1, a gene downstream of AhR. We investigated the possibility that A-to-I RNA editing creates miRNA targeting sites in the AhR mRNA and found that the miR-378-dependent down-regulation of AhR was abolished by ADAR1 knockdown. These results indicated that the ADAR1-mediated down-regulation of AhR could be attributed to the creation of a miR-378 recognition site in the AhR 3-UTR. The interindividual differences in the RNA editing levels within the AhR 3-UTR in a panel of 32 human liver samples were relatively small, whereas the differences in ADAR1 expression were large (220-fold). In the human liver samples a significant inverse association was observed between the miR-378 and AhR protein levels, suggesting that the RNA-editingdependent down-regulation of AhR by miR-378 contributes to the variability in the constitutive hepatic expression of AhR. In conclusion, this study uncovered for the first time that A-to-I RNA editing modulates the potency of xenobiotic metabolism in the human liver.

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“…We find that ADAR interacts with mRNAs encoding transcriptional regulators, zinc-finger proteins, and components of the secretory pathway. A similar approach has been taken to identify ADAR substrates in human B cells (Wang et al 2013), and the results indicate that human ADAR1 also targets mRNAs encoding zinc-finger proteins. It is remarkable that Xenopus and human ADAR target similar classes of mRNAs, as the vast majority of Ato-I editing events in the human transcriptome occur in primate-specific Alu elements, which are absent in frogs.…”

Section: Adar-endornps: Adar-rnps Containing Endogenous Rnasmentioning

confidence: 99%

“…We find that the ADAR-associated mRNAs are enriched for transcripts encoding transcriptional regulators, zinc-finger proteins, and components of the secretory pathway (Supplemental Table 2). It has been demonstrated that editing targets in human B cells are also enriched for mRNAs encoding zinc-finger proteins (Wang et al 2013), suggesting that ADAR plays a conserved role in regulating this class of mRNAs. The finding that ADAR-associated mRNAs tend to encode transcription factors and proteins involved in signal transduction led us to hypothesize that ADAR might sequester and translationally repress maternal transcripts needed later in development.…”

Section: Adar Associates With Endogenous Xenopus Mrnasmentioning

confidence: 99%

Evidence for multiple, distinct ADAR-containing complexes in Xenopus laevis

Schweidenback

Emerman

Jambhekar

et al. 2014

RNA

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ADAR (adenosine deaminase acting on RNA) is an RNA-editing enzyme present in most metazoans that converts adenosines in double-stranded RNA targets into inosines. Although the RNA targets of ADAR-mediated editing have been extensively cataloged, our understanding of the cellular function of such editing remains incomplete. We report that long, doublestranded RNA added to Xenopus laevis egg extract is incorporated into an ADAR-containing complex whose protein components resemble those of stress granules. This complex localizes to microtubules, as assayed by accumulation on meiotic spindles. We observe that the length of a double-stranded RNA influences its incorporation into the microtubule-localized complex. ADAR forms a similar complex with endogenous RNA, but the endogenous complex fails to localize to microtubules. In addition, we characterize the endogenous, ADAR-associated RNAs and discover that they are enriched for transcripts encoding transcriptional regulators, zinc-finger proteins, and components of the secretory pathway. Interestingly, association with ADAR correlates with previously reported translational repression in early embryonic development. This work demonstrates that ADAR is a component of two, distinct ribonucleoprotein complexes that contain different types of RNAs and exhibit diverse cellular localization patterns. Our findings offer new insight into the potential cellular functions of ADAR.

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ADAR Regulates RNA Editing, Transcript Stability, and Gene Expression

Cited by 180 publications

References 53 publications

The emerging role of RNA editing in plasticity

The emerging role of RNA editing in plasticity

RNA Editing Modulates Human Hepatic Aryl Hydrocarbon Receptor Expression by Creating MicroRNA Recognition Sequence

Evidence for multiple, distinct ADAR-containing complexes in Xenopus laevis

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