Specific cleavage of hyper-edited dsRNAs

Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK
The EMBO Journal (Impact Factor: 10.43). 09/2001; 20(15):4243-52. DOI: 10.1093/emboj/20.15.4243
Source: PubMed


Extended double-stranded DNA (dsRNA) duplexes can be hyper-edited by adenosine deaminases that act on RNA (ADARs). Long uninterrupted dsRNA is relatively uncommon in cells, and is frequently associated with infection by DNA or RNA viruses. Moreover, extensive adenosine to inosine editing has been reported for various viruses. A number of cellular antiviral defence strategies are stimulated by dsRNA. An additional mechanism to remove dsRNA from cells may involve hyper-editing of dsRNA by ADARs, followed by targeted cleavage. We describe here a cytoplasmic endonuclease activity that specifically cleaves hyper-edited dsRNA. Cleavage occurs at specific sites consisting of alternating IU and UI base pairs. In contrast, unmodified dsRNA and even deaminated dsRNAs that contain four consecutive IU base pairs are not cleaved. Moreover, dsRNAs in which alternating IU and UI base pairs are replaced by isomorphic GU and UG base pairs are not cleaved. Thus, the cleavage of deaminated dsRNA appears to require an RNA structure that is unique to hyper-edited RNA, providing a molecular target for the disposal of hyper-edited viral RNA.

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Available from: Christopher W J Smith, Jul 10, 2014
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    • "We also did not find mutations in the virions released into the culture supernatant, suggesting that the edited RNA may not be suitable for virus assembly. The existence of ribonuclease specific for inosine-containing RNA has been described, leading to the possibility that edited HIV-1 RNA is rapidly destroyed [38]. These observations may account for the absence of the mutated RNA in the cells or culture supernatants. "
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    • "It was suggested that inosine-containing transcripts are subject to specific regulation, affecting the fate of the RNA molecule (Rueter et al. 1999; Scadden and Smith 2001; Zhang and Carmichael 2001; Prasanth et al. 2005; Liang and Landweber 2007; Scadden 2007). However, given the wide scope of Alu editing in the human transcriptome , a large fraction of human transcripts contains inosines, suggesting that additional factors must be involved in these RNA regulations. "
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    • "RNA editing: in this mechanism, RNAs that are completely, or largely, double-stranded experience deamination of adenosine to inosine [44]. The editing of long, perfect RNA duplexes can result in their nuclear retention [45] or cytoplasmic degradation [46]. "
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