title: The RISC subunit Tudor-SN binds to hyper-edited double-stranded RNA and promotes its cleavage.
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.
authors.affiliation: Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK. adjs@bioc.cam.ac.uk
authors.forename: A D J
authors.initials: AD
authors.lastname: Scadden
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D017931:DNA Primers; D008836:Micrococcal Nuclease / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017393:RNA Editing / Q000235:genetics; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics* / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000502:physiology
chemical_list: D017931:DNA Primers; D021122:Protein Subunits; D012330:RNA, Double-Stranded; D034743:RNA-Induced Silencing Complex; D029867:Xenopus Proteins; D008836:Micrococcal Nuclease; D000243:Adenosine Deaminase