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PMID: 11483527 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Specific cleavage of hyper-edited dsRNAs.

The EMBO journal ·Vol. 20 ·No. 15 ·2001-08-01 ·Pages 4243-52

Scadden AD, Smith CW

Abstract

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.

MeSH Terms
Adenosine Deaminase/metabolism Animals Base Pairing Base Sequence Cytoplasm/enzymology Guanine HeLa Cells Humans Molecular Sequence Data RNA Editing RNA, Double-Stranded/metabolism RNA-Binding Proteins Ribonucleases/metabolism Substrate Specificity Uracil Xenopus laevis/genetics
Chemicals
RNA, Double-Stranded RNA-Binding Proteins Uracil Guanine Ribonucleases ADARB1 protein, human Adenosine Deaminase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Scadden A D
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK
Smith C W
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.15.4243
Published
2001-08-01
Pages
4243-52
Language
English
Region
England
NLM ID
8208664
PMCID
PMC149145
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.15.4243 PMC Full Text View journal details
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