title: Modulation of ADAR1 editing activity by Z-RNA in vitro.
abstract: RNA editing by A-to-I modification has been recognized as an important molecular mechanism for generating RNA and protein diversity. In mammals, it is mediated by a family of adenosine deaminases that act on RNAs (ADARs). The large version of the editing enzyme ADAR1 (ADAR1-L), expressed from an interferon-responsible promoter, has a Z-DNA/Z-RNA binding domain at its N-terminus. We have tested the in vitro ability of the enzyme to act on a 50 bp segment of dsRNA with or without a Z-RNA forming nucleotide sequence. A-to-I editing efficiency is markedly enhanced in presence of the sequence favoring Z-RNA. In addition, an alteration in the pattern of modification along the RNA duplex becomes evident as reaction times decrease. These results suggest that the local conformation of dsRNA molecules might be an important feature for target selectivity by ADAR1 and other proteins with Z-RNA binding domains.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Koeris
authors.forename: Lars
authors.initials: L
authors.lastname: Funke
authors.forename: Jay
authors.initials: J
authors.lastname: Shrestha
authors.forename: Alexander
authors.initials: A
authors.lastname: Rich
authors.forename: Stefan
authors.initials: S
authors.lastname: Maas
mesh_terms: D000243:Adenosine Deaminase / Q000378:metabolism*; D002460:Cell Line; D003627:Data Interpretation, Statistical; D006801:Humans; D009690:Nucleic Acid Conformation; D017393:RNA Editing; D012330:RNA, Double-Stranded / Q000737:chemistry* / Q000378:metabolism*; D016601:RNA-Binding Proteins; D013379:Substrate Specificity
chemical_list: D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase