ADAR2-mediated Editing of RNA Substrates in the Nucleolus is Inhibited by C/D Small Nucleolar RNAs

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2005 Jun 9

PMID 15939761

Citations 110

Authors

Patrice Vitali

Eugenia Basyuk

Elodie Le Meur

Edouard Bertrand

Francoise Muscatelli

Jerome Cavaille

Alexander Huttenhofer

Affiliations

Soon will be listed here.

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.

Citing Articles

Small Nucleolar RNAs and the Brain: Growing Evidence Supporting Their Role in Psychiatric Disorders.

Salles J, Lin R, Turecki G Biol Psychiatry Glob Open Sci. 2025; 5(2):100415.

PMID: 39867567 PMC: 11758842. DOI: 10.1016/j.bpsgos.2024.100415.

snoRNA-facilitated protein secretion revealed by transcriptome-wide snoRNA target identification.

Liu B, Wu T, Miao B, Ji F, Liu S, Wang P Cell. 2024; 188(2):465-483.e22.

PMID: 39579764 PMC: 11761385. DOI: 10.1016/j.cell.2024.10.046.

Loss of ADAR1 protein induces changes in small RNA landscape in hepatocytes.

Roucova K, Vopalensky V, Masek T, Del Llano E, Provaznik J, Landry J RNA. 2024; 30(9):1164-1183.

PMID: 38844344 PMC: 11331409. DOI: 10.1261/rna.080097.124.

RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy.

Liu W, Zheng S, Li T, Fei Y, Wang C, Zhang S Signal Transduct Target Ther. 2024; 9(1):70.

PMID: 38531882 PMC: 10966055. DOI: 10.1038/s41392-024-01777-5.

Lessons from discovery of true ADAR RNA editing sites in a human cell line.

Wang F, Cao H, Xia Q, Liu Z, Wang M, Gao F BMC Biol. 2023; 21(1):160.

PMID: 37468903 PMC: 10357658. DOI: 10.1186/s12915-023-01651-w.

References

Rueter S, Dawson T, Emeson R . Regulation of alternative splicing by RNA editing. Nature. 1999; 399(6731):75-80. DOI: 10.1038/19992. View

Keller W, Wolf J, Gerber A . Editing of messenger RNA precursors and of tRNAs by adenosine to inosine conversion. FEBS Lett. 1999; 452(1-2):71-6. DOI: 10.1016/s0014-5793(99)00590-6. View

Easterwood L, Kamilar G, Beal P . Synthetic substrate analogs for the RNA-editing adenosine deaminase ADAR-2. Nucleic Acids Res. 1999; 27(14):2912-7. PMC: 148506. DOI: 10.1093/nar/27.14.2912. View

Ganot P, Jady B, Bortolin M, Darzacq X, Kiss T . Nucleolar factors direct the 2'-O-ribose methylation and pseudouridylation of U6 spliceosomal RNA. Mol Cell Biol. 1999; 19(10):6906-17. PMC: 84686. DOI: 10.1128/MCB.19.10.6906. View

Herrick-Davis K, Grinde E, Niswender C . Serotonin 5-HT2C receptor RNA editing alters receptor basal activity: implications for serotonergic signal transduction. J Neurochem. 1999; 73(4):1711-7. DOI: 10.1046/j.1471-4159.1999.731711.x. View

Andersen J, Lam Y, Leung A, Ong S, Lyon C, Lamond A . Nucleolar proteome dynamics. Nature. 2005; 433(7021):77-83. DOI: 10.1038/nature03207. View

Runte M, Varon R, Horn D, Horsthemke B, Buiting K . Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader-Willi syndrome. Hum Genet. 2004; 116(3):228-30. DOI: 10.1007/s00439-004-1219-2. View

Melcher T, Maas S, Herb A, Sprengel R, Seeburg P, Higuchi M . A mammalian RNA editing enzyme. Nature. 1996; 379(6564):460-4. DOI: 10.1038/379460a0. View

Maas S, Melcher T, Herb A, Seeburg P, Keller W, Krause S . Structural requirements for RNA editing in glutamate receptor pre-mRNAs by recombinant double-stranded RNA adenosine deaminase. J Biol Chem. 1996; 271(21):12221-6. DOI: 10.1074/jbc.271.21.12221. View

10.

Kiss-Laszlo Z, Henry Y, Bachellerie J, Caizergues-Ferrer M, Kiss T . Site-specific ribose methylation of preribosomal RNA: a novel function for small nucleolar RNAs. Cell. 1996; 85(7):1077-88. DOI: 10.1016/s0092-8674(00)81308-2. View

11.

Canton H, Emeson R, Barker E, Backstrom J, Lu J, Chang M . Identification, molecular cloning, and distribution of a short variant of the 5-hydroxytryptamine2C receptor produced by alternative splicing. Mol Pharmacol. 1996; 50(4):799-807. View

12.

Cavaille J, Nicoloso M, Bachellerie J . Targeted ribose methylation of RNA in vivo directed by tailored antisense RNA guides. Nature. 1996; 383(6602):732-5. DOI: 10.1038/383732a0. View

13.

Tiveron M, HIRSCH M, Brunet J . The expression pattern of the transcription factor Phox2 delineates synaptic pathways of the autonomic nervous system. J Neurosci. 1996; 16(23):7649-60. PMC: 6579082. View

14.

Melcher T, Maas S, Herb A, Sprengel R, Higuchi M, Seeburg P . RED2, a brain-specific member of the RNA-specific adenosine deaminase family. J Biol Chem. 1996; 271(50):31795-8. DOI: 10.1074/jbc.271.50.31795. View

15.

Burns C, Chu H, Rueter S, Hutchinson L, Canton H, Sanders-Bush E . Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature. 1997; 387(6630):303-8. DOI: 10.1038/387303a0. View

16.

Shaw P, Beven A, Leader D, Brown J . Localization and processing from a polycistronic precursor of novel snoRNAs in maize. J Cell Sci. 1998; 111 ( Pt 15):2121-8. DOI: 10.1242/jcs.111.15.2121. View

17.

Niswender C, Copeland S, Herrick-Davis K, Emeson R, Sanders-Bush E . RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J Biol Chem. 1999; 274(14):9472-8. DOI: 10.1074/jbc.274.14.9472. View

18.

Wang Q, OBrien P, Chen C, Cho D, Murray J, Nishikura K . Altered G protein-coupling functions of RNA editing isoform and splicing variant serotonin2C receptors. J Neurochem. 2000; 74(3):1290-300. DOI: 10.1046/j.1471-4159.2000.741290.x. View

19.

Reenan R, Hanrahan C, Ganetzky B . The mle(napts) RNA helicase mutation in drosophila results in a splicing catastrophe of the para Na+ channel transcript in a region of RNA editing. Neuron. 2000; 25(1):139-49. DOI: 10.1016/s0896-6273(00)80878-8. View

20.

Phair R, Misteli T . High mobility of proteins in the mammalian cell nucleus. Nature. 2000; 404(6778):604-9. DOI: 10.1038/35007077. View