title: ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs.
abstract: Posttranscriptional, site-specific adenosine to inosine (A-to-I) base conversions, designated as RNA editing, play significant roles in generating diversity of gene expression. However, little is known about how and in which cellular compartments RNA editing is controlled. Interestingly, the two enzymes that catalyze RNA editing, adenosine deaminases that act on RNA (ADAR) 1 and 2, have recently been demonstrated to dynamically associate with the nucleolus. Moreover, we have identified a brain-specific small RNA, termed MBII-52, which was predicted to function as a nucleolar C/D RNA, thereby targeting an A-to-I editing site (C-site) within the 5-HT2C serotonin receptor pre-mRNA for 2'-O-methylation. Through the subcellular targeting of minigenes that contain natural editing sites, we show that ADAR2- but not ADAR1-mediated RNA editing occurs in the nucleolus. We also demonstrate that MBII-52 forms a bona fide small nucleolar ribonucleoprotein particle that specifically decreases the efficiency of RNA editing by ADAR2 at the targeted C-site. Our data are consistent with a model in which C/D small nucleolar RNA might play a role in the regulation of RNA editing.
authors.affiliation: Laboratoire de Biologie Moléculaire des Eucaryotes, Centre National de la Recherche Scientifique, UMR 5095, Institut Fédératif de Recherche 109, 31062 Cedex Toulouse, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Vitali
authors.forename: Eugenia
authors.initials: E
authors.lastname: Basyuk
authors.forename: Elodie
authors.initials: E
authors.lastname: Le Meur
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
authors.forename: Françoise
authors.initials: F
authors.lastname: Muscatelli
authors.forename: Jérôme
authors.initials: J
authors.lastname: Cavaillé
authors.forename: Alexander
authors.initials: A
authors.lastname: Huttenhofer
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002451:Cell Compartmentation / Q000235:genetics; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D017393:RNA Editing / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism
chemical_list: D012322:RNA Precursors; D012330:RNA, Double-Stranded; D020537:RNA, Small Nucleolar; D016601:RNA-Binding Proteins; D044405:Receptor, Serotonin, 5-HT2C; D018091:Receptors, AMPA; D020718:Ribonucleoproteins, Small Nucleolar; C115953:glutamate receptor type B; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase