Human endonuclease V is a ribonuclease specific for inosine-containing RNA

Morita, Yoko; Shibutani, Toshihiro; Nakanishi, Nozomi; Nishikura, Kazuko; Iwai, Shigenori; Kuraoka, Isao

doi:10.1038/ncomms3273

Cited by 92 publications

(115 citation statements)

References 39 publications

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“…Alternatively, hyperediting in 3 0 UTR can recruit inosine-specific nucleases and subsequently leads to the edited target degradation. Both human endonuclease V and Tudor staphylococcal nuclease have been demonstrated to interact with hyperedited dsRNAs and promote its cleavage (29,30). As for the location of hyperedited RNA, nuclear retention of edited RNAs has been reported by a P54 nrb containing tri-protein complex (31).…”

Section: Decoding Of A-to-i Editingmentioning

confidence: 99%

RNA Editome Imbalance in Hepatocellular Carcinoma

et al. 2014

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Adenosine-to-inosine conversion (A-to-I editing), a posttranscriptional modification on RNA, contributes to extensive transcriptome diversity. A-to-I editing is a hydrolytic deamination process, catalyzed by adenosine deAminase acting on double-stranded RNA (ADAR) family of enzymes. ADARs are essential for normal mammalian development, and disturbance in RNA editing has been implicated in various pathologic disorders, including cancer. Thanks to next-generation sequencing, rich databases of transcriptome evolution for cancer development at the resolution of single nucleotide have been generated. Extensive bioinformatic analysis revealed a complex picture of RNA editing change during transformation. Cancer displayed global hypoediting of Alurepetitive elements with gene-specific editing pattern. In particular, hepatocellular carcinoma editome is severely disrupted and characterized by hyper-and hypoediting of different genes, such as hyperedited AZIN1 (antizyme inhibitor 1) and FLNB (filamin B, b) and hypoedited COPA (coatomer protein complex, subunit a). In hepatocellular carcinoma, not only the recoding editing in exons, but also the editing in noncoding regions (e.g., Alu-repetitive elements and microRNA) displays such complex editing pattern with site-specific editing trend. In this review, we will discuss current research progress on the involvement of abnormal A-to-I editing in cancer development, more specifically on hepatocellular carcinoma. Cancer Res; 74(5); 1301-6. Ó2014 AACR.

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Section: Decoding Of A-to-i Editingmentioning

confidence: 99%

RNA Editome Imbalance in Hepatocellular Carcinoma

et al. 2014

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“…Perfectly paired dsRNA substrates with or without inosines are resistant to cTSN cleavage. An inosine-specific ribonuclease (Endo V) has previously been characterized (Morita et al, 2013), and we conclude that TSN is not inosine-specific but is a structure-specific ribonuclease that targets single-stranded RNA and dsRNA with loose regions. Presence of long perfect dsRNA molecules in the cell usually indicates viral infection and invading nucleic acids.…”

Section: Discussionmentioning

confidence: 99%

Tudor staphylococcal nuclease is a structure-specific ribonuclease that degrades RNA at unstructured regions during microRNA decay

Yang

Shi

et al. 2018

RNA

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ABSTRACT-binding residues in these two domains strongly impaired its ribonuclease activity. We further show by small-angle X-ray scattering that rice osTSN has a flexible two-lobed structure with open to closed conformations, indicating that TSN may change its conformation upon RNA binding. We conclude that TSN is a structure-specific ribonuclease targeting not only single-stranded RNA, but also unstructured regions of double-stranded RNA. This study provides the molecular basis for how TSN cooperates with RNA editing to eliminate duplex RNA in cell defense, and how TSN selects and degrades RNA during microRNA decay.

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“…In non-coding regions, the vast majority of A-to-I RNA editing sites are in repetitive Alu elements embedded in 3' untranslated regions (3'UTRs) (Farajollahi and Maas 2010) and have unknown functional relevance. Previously described fates of mRNAs undergoing extensive A-to-I editing at their 3'UTRs are via RNA editingdependent mechanisms including nuclear retention, nuclease-mediated degradation, and alteration of microRNA (miRNA) targeting (Zhang and Carmichael 2001;Scadden 2005;Kawahara et al 2007b;Morita et al 2013), thereby influencing the expression of target genes.ADARs have been found to be critical for normal development through and/or beyond A-to-I editing in different genetically modified animal models. Notably, the early post-natal lethality of the Adar2-/-mouse could be rescued by the ectopic expression of edited glutamate receptor subunit B (GluR-B), suggesting the editing activity of ADAR2 is essential for normal mouse development (Higuchi et al 2000).…”

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confidence: 99%

An RNA editing/binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer

Liu

Song

Chan

et al. 2016

Preprint

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Adenosine-to-inosine (A-to-I) editing, catalysed by Adenosine DeAminases acting on double-stranded RNA (dsRNA) (ADAR), occurs predominantly in the 3' untranslated regions (3'UTRs). Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3'UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor as an exemplary target gene, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and dsRNA binding functions. ADARs interact with Dicer to augment the processing of pre-miR-27a to mature miR-27a. Consequently, mature miR-27a targets the METTL7A 3'UTR to repress its expression level. In sum, our study unveils that the extensive 3'UTR editing is merely a footprint of ADAR binding, and is dispensable for the regulation of at least a subset of target genes. Instead, ADARs contribute to cancer progression by regulating cancer-related gene expression through their non-canonical functions independent of RNA editing and dsRNA binding.The functional significance of ADARs is much more diverse than previously appreciated and this gene regulatory function of ADARs is most likely to be of higher importance than the best-studied editing function. This novel non-editing side of ADARs opens another door to target cancer. This study is timely and represents a major break-through in the field of ADAR gene regulation and cancer biology. (215 words)peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/062778 doi: bioRxiv preprint first posted online Qi, L., et al., Page 3 Adenosine DeAminases acting on dsRNA (ADAR) are highly conserved family of enzymes catalysing adenosine to inosine deamination (A-to-I editing) (Bass and Weintraub 1988;Wagner et al. 1989).There are 3 ADAR proteins (ADAR1, ADAR2 and ADAR3) in humans which all share a common modular structure characterized by 2 to 3 N-terminal dsRNA binding domains (dsRBDs) and a conserved C-terminal catalytic deaminase domain (Nishikura 2010;Qi et al. 2014). Being the beststudied function associated with ADAR1 and ADAR2 (ADARs), A-to-I RNA editing contributes to multi-level gene regulation depending on where it occurs. ADAR3, which has no documented deaminase activity, is only expressed in central nervous system (Melcher et al. 1996). In coding regions, A-to-I RNA editing can lead to a codon change and the consequent alterations of proteincoding sequences since inosine is interpreted by the ribosome as guanosine (Nishikura 2010). The differential editing frequencies of these recoding sites are found to impact on human diseases such as neurological diseases and cancer (Martinez et al. 2008;Chen et al. 2013;Galeano et al. 2013;Han et al. 2014;Paz-Yaacov et al. 2015;Villa et al. 2015). In non-coding regions, the vast majority of A-to-I RNA editing sites are in repetitive Alu elements embedded in 3' untranslated regions (3'UTRs) (Fa...

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Human endonuclease V is a ribonuclease specific for inosine-containing RNA

Cited by 92 publications

References 39 publications

RNA Editome Imbalance in Hepatocellular Carcinoma

RNA Editome Imbalance in Hepatocellular Carcinoma

Tudor staphylococcal nuclease is a structure-specific ribonuclease that degrades RNA at unstructured regions during microRNA decay

An RNA editing/binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer

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