title: An ADAR that edits transcripts encoding ion channel subunits functions as a dimer.
abstract: In this report, we establish that Drosophila ADAR (adenosine deaminase acting on RNA) forms a dimer on double-stranded (ds) RNA, a process essential for editing activity. The minimum region required for dimerization is the N-terminus and dsRNA-binding domain 1 (dsRBD1). Single point mutations within dsRBD1 abolish RNA-binding activity and dimer formation. These mutations and glycerol gradient analysis indicate that binding to dsRNA is important for dimerization. However, dimerization can be uncoupled from dsRNA-binding activity, as a deletion of the N-terminus (amino acids 1-46) yields a monomeric ADAR that retains the ability to bind dsRNA but is inactive in an editing assay, demonstrating that ADAR is only active as a dimer. Different isoforms of ADAR with different editing activities can form heterodimers and this can have a significant effect on editing in vitro as well as in vivo. We propose a model for ADAR dimerization whereby ADAR monomers first contact dsRNA; however, it is only when the second monomer binds and a dimer is formed that deamination occurs.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Gallo
authors.forename: Liam P
authors.initials: LP
authors.lastname: Keegan
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Ring
authors.forename: Mary A
authors.initials: MA
authors.lastname: O'Connell
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D019281:Dimerization; D004330:Drosophila; D007473:Ion Channels / Q000235:genetics*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D007473:Ion Channels; D012333:RNA, Messenger; D000243:Adenosine Deaminase