Nucleolar localization of aprataxin is dependent on interaction with nucleolin and on active ribosomal DNA transcription

Becherel, Olivier J., Gueven, Nuri, Birrell, Geoff W., Schreiber, Valérie, Suraweera, Amila, Jakob, Burkhard, Taucher-Scholz, Gisela and Lavin, Martin F. (2006) Nucleolar localization of aprataxin is dependent on interaction with nucleolin and on active ribosomal DNA transcription. Human Molecular Genetics, 15 14: 2239-2249. doi:10.1093/hmg/ddl149


Author Becherel, Olivier J.
Gueven, Nuri
Birrell, Geoff W.
Schreiber, Valérie
Suraweera, Amila
Jakob, Burkhard
Taucher-Scholz, Gisela
Lavin, Martin F.
Title Nucleolar localization of aprataxin is dependent on interaction with nucleolin and on active ribosomal DNA transcription
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2006-07
Sub-type Article (original research)
DOI 10.1093/hmg/ddl149
Open Access Status
Volume 15
Issue 14
Start page 2239
End page 2249
Total pages 11
Editor A. Wynshaw-Boris
Place of publication Oxford
Publisher Oxford University Press
Collection year 2006
Language eng
Subject CX
320305 Medical Biochemistry - Proteins and Peptides
730104 Nervous system and disorders
C1
Abstract The APTX gene, mutated in patients with the neurological disorder ataxia with oculomotor apraxia type 1 (AOA1), encodes a novel protein aprataxin. We describe here, the interaction and interdependence between aprataxin and several nucleolar proteins, including nucleolin, nucleophosmin and upstream binding factor-1 (UBF-1), involved in ribosomal RNA (rRNA) synthesis and cellular stress signalling. Interaction between aprataxin and nucleolin occurred through their respective N-terminal regions. In AOA1 cells lacking aprataxin, the stability of nucleolin was significantly reduced. On the other hand, down-regulation of nucleolin by RNA interference did not affect aprataxin protein levels but abolished its nucleolar localization suggesting that the interaction with nucleolin is involved in its nucleolar targeting. GFP-aprataxin fusion protein co-localized with nucleolin, nucleophosmin and UBF-1 in nucleoli and inhibition of ribosomal DNA transcription altered the distribution of aprataxin in the nucleolus, suggesting that the nature of the nucleolar localization of aprataxin is also dependent on ongoing rRNA synthesis. In vivo rRNA synthesis analysis showed only a minor decrease in AOA1 cells when compared with controls cells. These results demonstrate a cross-dependence between aprataxin and nucleolin in the nucleolus and while aprataxin does not appear to be directly involved in rRNA synthesis its nucleolar localization is dependent on this synthesis.
Keyword Biochemistry & Molecular Biology
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 09:00:18 EST