title: Regulation of glutamate receptor B pre-mRNA splicing by RNA editing.
abstract: RNA-editing enzymes of the ADAR family convert adenosines to inosines in double-stranded RNA substrates. Frequently, editing sites are defined by base-pairing of the editing site with a complementary intronic region. The glutamate receptor subunit B (GluR-B) pre-mRNA harbors two such exonic editing sites termed Q/R and R/G. Data from ADAR knockout mice and in vitro editing assays suggest an intimate connection between editing and splicing of GluR-B pre-mRNA. By comparing the events at the Q/R and R/G sites, we can show that editing can both stimulate and repress splicing efficiency. The edited nucleotide, but not ADAR binding itself, is sufficient to exert this effect. The presence of an edited nucleotide at the R/G site reduces splicing efficiency of the adjacent intron facilitating alternative splicing events occurring downstream of the R/G site. Lack of editing inhibits splicing at the Q/R site. Editing of both the Q/R nucleotide and an intronic editing hotspot are required to allow efficient splicing. Inefficient intron removal may ensure that only properly edited mRNAs become spliced and exported to the cytoplasm.
authors.affiliation: Department of Chromosome Biology, Max F. Perutz Laboratories, University of Vienna, Dr Bohr-Gasse 1, A-1030 Vienna, Austria.
authors.forename: Vera K
authors.initials: VK
authors.lastname: Schoft
authors.forename: Sandy
authors.initials: S
authors.lastname: Schopoff
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jantsch
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D017930:Genes, Reporter; D006801:Humans; D007288:Inosine / Q000032:analysis; D051379:Mice; D017393:RNA Editing; D012322:RNA Precursors / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism
chemical_list: D012322:RNA Precursors; D012333:RNA, Messenger; D018091:Receptors, AMPA; C115953:glutamate receptor type B; D007288:Inosine