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.
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6 June 2005
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June 06 2005
ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs
Patrice Vitali,
Patrice Vitali
1Laboratoire de Biologie Moléculaire des Eucaryotes, Centre National de la Recherche Scientifique (CNRS), UMR 5095, Institut Fédératif de Recherche (IFR) 109, 31062 Cedex Toulouse, France
3Innbruck Biocentre, Division of Genomics and RNomics, Innsbruck Medical University, 6020 Innsbruck, Austria
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Eugenia Basyuk,
Eugenia Basyuk
2Institut de Genetique Moleculaire de Montpellier, CNRS, UMR 5535, Université Montpellier II, IFR 122, 34293 Montpellier Cedex 5, France
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Elodie Le Meur,
Elodie Le Meur
4Institut de Biologie du Développement de Marseille, Campus de Luminy, 13288 Cedex 9, Marseille, France
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Edouard Bertrand,
Edouard Bertrand
2Institut de Genetique Moleculaire de Montpellier, CNRS, UMR 5535, Université Montpellier II, IFR 122, 34293 Montpellier Cedex 5, France
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Françoise Muscatelli,
Françoise Muscatelli
4Institut de Biologie du Développement de Marseille, Campus de Luminy, 13288 Cedex 9, Marseille, France
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Jérôme Cavaillé,
Jérôme Cavaillé
1Laboratoire de Biologie Moléculaire des Eucaryotes, Centre National de la Recherche Scientifique (CNRS), UMR 5095, Institut Fédératif de Recherche (IFR) 109, 31062 Cedex Toulouse, France
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Alexander Huttenhofer
Alexander Huttenhofer
3Innbruck Biocentre, Division of Genomics and RNomics, Innsbruck Medical University, 6020 Innsbruck, Austria
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Patrice Vitali
1Laboratoire de Biologie Moléculaire des Eucaryotes, Centre National de la Recherche Scientifique (CNRS), UMR 5095, Institut Fédératif de Recherche (IFR) 109, 31062 Cedex Toulouse, France
3Innbruck Biocentre, Division of Genomics and RNomics, Innsbruck Medical University, 6020 Innsbruck, Austria
Eugenia Basyuk
2Institut de Genetique Moleculaire de Montpellier, CNRS, UMR 5535, Université Montpellier II, IFR 122, 34293 Montpellier Cedex 5, France
Elodie Le Meur
4Institut de Biologie du Développement de Marseille, Campus de Luminy, 13288 Cedex 9, Marseille, France
Edouard Bertrand
2Institut de Genetique Moleculaire de Montpellier, CNRS, UMR 5535, Université Montpellier II, IFR 122, 34293 Montpellier Cedex 5, France
Françoise Muscatelli
4Institut de Biologie du Développement de Marseille, Campus de Luminy, 13288 Cedex 9, Marseille, France
Jérôme Cavaillé
1Laboratoire de Biologie Moléculaire des Eucaryotes, Centre National de la Recherche Scientifique (CNRS), UMR 5095, Institut Fédératif de Recherche (IFR) 109, 31062 Cedex Toulouse, France
Alexander Huttenhofer
3Innbruck Biocentre, Division of Genomics and RNomics, Innsbruck Medical University, 6020 Innsbruck, Austria
Correspondence to Jérôme Cavaillé: [email protected]
Abbreviations used in this paper: ADAR, adenosine deaminases that act on RNA; CB, Cajal body; CMV, cytomegalo virus; dNTP, deoxynucleotide triphosphate; ds, double stranded; GluR, glutamate receptor; PWS, Prader-Willi syndrome; scaRNA, small CB-specific RNA; snoRNA, small nucleolar RNA.
Received:
November 22 2004
Accepted:
April 14 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 169 (5): 745–753.
Article history
Received:
November 22 2004
Accepted:
April 14 2005
Citation
Patrice Vitali, Eugenia Basyuk, Elodie Le Meur, Edouard Bertrand, Françoise Muscatelli, Jérôme Cavaillé, Alexander Huttenhofer; ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs . J Cell Biol 6 June 2005; 169 (5): 745–753. doi: https://doi.org/10.1083/jcb.200411129
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