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Published 6 June 2005. doi:10.1083/jcb.200411129
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 5, 745-753
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Article

ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D small nucleolar RNAs



Patrice Vitali1,3, Eugenia Basyuk2, Elodie Le Meur4, Edouard Bertrand2, Françoise Muscatelli4, Jérôme Cavaillé1, and Alexander Huttenhofer3

1 Laboratoire de Biologie Moléculaire des Eucaryotes, Centre National de la Recherche Scientifique (CNRS), UMR 5095, Institut Fédératif de Recherche (IFR) 109, 31062 Cedex Toulouse, France
2 Institut de Genetique Moleculaire de Montpellier, CNRS, UMR 5535, Université Montpellier II, IFR 122, 34293 Montpellier Cedex 5, France
3 Innbruck Biocentre, Division of Genomics and RNomics, Innsbruck Medical University, 6020 Innsbruck, Austria
4 Institut de Biologie du Développement de Marseille, Campus de Luminy, 13288 Cedex 9, Marseille, France

Correspondence to Jérôme Cavaillé: cavaille{at}ibcg.biotoul.fr

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.

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.


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