Abstract
Long perfect double-stranded RNA (dsRNA) molecules play a role in various cellular pathways. dsRNA may undergo extensive covalent modification (hyper-editing) by adenosine deaminases that act on RNA (ADARs), resulting in conversion of up to 50% of adenosine residues to inosine (I). Alternatively, dsRNA may trigger RNA interference (RNAi), resulting in silencing of the cognate mRNA. These two pathways have previously been shown to be antagonistic. We show a novel interaction between components of the ADAR and RNAi pathways. Tudor staphylococcal nuclease (Tudor-SN) is a subunit of the RNA-induced silencing complex, which is central to the mechanism of RNAi. Here we show that Tudor-SN specifically interacts with and promotes cleavage of model hyper-edited dsRNA substrates containing multiple I·U and U·I pairs. This interaction suggests a novel unsuspected interplay between the two pathways that is more complex than mutual antagonism.
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Acknowledgements
I would like to thank G. Hannon, S. Holmes, N. Minshall, R. Allison, L. Colegrove, A. Devaux and C. Gooding for gifts of reagents, and the Cambridge Centre for Proteomics (in particular K. Lilley) for protein analyses. I would like to thank C. Smith for helpful discussions and critically reading the manuscript, and also N. Proudfoot and M. O'Connell for comments on the manuscript. This work was supported by a Research Career Development Fellowship from the Wellcome Trust. The Cambridge Centre for Proteomics facility at Cambridge was funded by the UK Biotechnology and Biological Sciences Research Council's Investigating Gene Function Initiative.
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Scadden, A. The RISC subunit Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage. Nat Struct Mol Biol 12, 489–496 (2005). https://doi.org/10.1038/nsmb936
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DOI: https://doi.org/10.1038/nsmb936
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