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Specific cleavage of hyper‐edited dsRNAs
Author(s) -
Scadden A.D.J.,
Smith Christopher W.J.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.15.4243
Subject(s) - rna silencing , biology , rna , rna editing , inosine , cleavage (geology) , base pair , endonuclease , dna , microbiology and biotechnology , genetics , adenosine , biochemistry , rna interference , gene , paleontology , fracture (geology)
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.