Editing independent effects of ADARs on the miRNA/siRNA pathways

Heale, Bret S.E.; Keegan, Liam P.; McGurk, Leeanne; Michlewski, Gracjan; Brindle, James; Stanton, Chloe; Cáceres, Javier F.; O’Connell, Mary A.

doi:10.1038/emboj.2009.244

Cited by 166 publications

(194 citation statements)

References 55 publications

(89 reference statements)

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“…Our data revealed that RNA editing has little correlation with mRNA expression changes in ADAR1 KD H9 cells (Supplementary information, Figure S4 and data not shown), which is in consistency with recent reports in other organisms [18][19][20]. We hypothesized that ADAR1 deficiency may lead to an altered miRNA repertoire, which in turn regulates mRNA expression in H9 cells and during differentiation.…”

Section: Adar1 Knockdown Dramatically Alters Mirna Repertoiressupporting

confidence: 91%

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ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner

et al. 2015

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Adenosine deaminases acting on RNA (ADARs) are involved in adenosine-to-inosine RNA editing and are implicated in development and diseases. Here we observed that ADAR1 deficiency in human embryonic stem cells (hESCs) significantly affected hESC differentiation and neural induction with widespread changes in mRNA and miRNA expression, including upregulation of self-renewal-related miRNAs, such as miR302s. Global editing analyses revealed that ADAR1 editing activity contributes little to the altered miRNA/mRNA expression in ADAR1-deficient hESCs upon neural induction. Genome-wide iCLIP studies identified that ADAR1 binds directly to pri-miRNAs to interfere with miRNA processing by acting as an RNA-binding protein. Importantly, aberrant expression of miRNAs and phenotypes observed in ADAR1-depleted hESCs upon neural differentiation could be reversed by an enzymatically inactive ADAR1 mutant, but not by the RNA-binding-null ADAR1 mutant. These findings reveal that ADAR1, but not its editing activity, is critical for hESC differentiation and neural induction by regulating miRNA biogenesis via direct RNA interaction.

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Section: Adar1 Knockdown Dramatically Alters Mirna Repertoiressupporting

confidence: 91%

“…Besides the catalytic activity of ADARs on miRNAs, it has been shown that ADARs can modulate the miR-NA/siRNA pathways independently of the editing activity in fly [19]. ADARs are also important for maintaining many small RNAs in C. elegans through both editing and non-editing activities [20].…”

Section: Introductionmentioning

confidence: 99%

ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner

et al. 2015

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“…A recent study showed that catalytically inactive ADAR1 and ADAR2 can modulate the micro RNA and siRNA pathways in Drosophila. 32 Similar functions might be expected for the inactive ADAR homologues in mammals. Catalytically inactive proteins might influence alternative splicing, hnRNA packaging or mRNA transport by their ability to bind dsRNA.…”

Section: Targets For Adenosine To Inosine Editingmentioning

confidence: 58%

Proteome diversification by adenosine to inosine RNA-editing

Pullirsch

Jantsch²

2010

RNA Biology

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“…Drosha cleavage of pri-mR-376a2 was inhibited by catalytically inactive ADAR2 because of ADAR2 binding [103]. This result indicates that other dsRNA binding proteins may bind to the pri-miRNA or pre-miRNA hairpin structures and affect the miRNA processing.…”

Section: Editing In Small Non-coding Rnasmentioning

confidence: 94%

ADAR-mediated RNA editing in non-coding RNA sequences

Yang

Zhou

Jin

2013

Sci. China Life Sci.

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Adenosine to inosine (A-to-I) RNA editing is the most abundant editing event in animals. It converts adenosine to inosine in double-stranded RNA regions through the action of the adenosine deaminase acting on RNA (ADAR) proteins. Editing of pre-mRNA coding regions can alter the protein codon and increase functional diversity. However, most of the A-to-I editing sites occur in the non-coding regions of pre-mRNA or mRNA and non-coding RNAs. Untranslated regions (UTRs) and introns are located in pre-mRNA non-coding regions, thus A-to-I editing can influence gene expression by nuclear retention, degradation, alternative splicing, and translation regulation. Non-coding RNAs such as microRNA (miRNA), small interfering RNA (siRNA) and long non-coding RNA (lncRNA) are related to pre-mRNA splicing, translation, and gene regulation. A-to-I editing could therefore affect the stability, biogenesis, and target recognition of non-coding RNAs. Finally, it may influence the function of non-coding RNAs, resulting in regulation of gene expression. This review focuses on the function of ADAR-mediated RNA editing on mRNA non-coding regions (UTRs and introns) and non-coding RNAs (miRNA, siRNA, and lncRNA).

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Editing independent effects of ADARs on the miRNA/siRNA pathways

Cited by 166 publications

References 55 publications

ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner

ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner

Proteome diversification by adenosine to inosine RNA-editing

ADAR-mediated RNA editing in non-coding RNA sequences

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