The Ccr4–Not complex is evolutionarily conserved and important for regulation of mRNA synthesis and decay. The composition of the yeast complex has been well described. Orthologues of the yeast Ccr4–Not components have been identified in human cells including multiple subunits with mRNA deadenylase activity. In the present study, we examine the composition of the human Ccr4–Not complex in an in-depth proteomic approach using stable cell lines expressing tagged CNOT proteins. We find at least four different variants of the human complex, consisting of seven stable core proteins and mutually exclusive associated mRNA deadenylase subunits. Interestingly, human CNOT4 is in a separate ~200 kDa complex. Furthermore, analyses of associated proteins indicate involvement of Ccr4–Not complexes in splicing, transport and localization of RNA molecules. Taken together, human Ccr4–Not complexes are heterogeneous in composition owing to differences in their deadenylase subunits, which may reflect the multi-functionality of these complexes in cellular processes.
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Research Article|
August 27 2009
Human Ccr4–Not complexes contain variable deadenylase subunits
Nga-Chi Lau;
Nga-Chi Lau
*Department of Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
†Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands
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Annemieke Kolkman;
Annemieke Kolkman
1
†Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands
‡Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands
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Frederik M. A. van Schaik;
Frederik M. A. van Schaik
*Department of Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
†Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands
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Klaas W. Mulder;
Klaas W. Mulder
§Epithelial Cell Biology Laboratory, Cancer Research UK Cambridge Research Institute, Li Ka-Shing Centre, Robinson Way, Cambridge CB2 0RE, U.K.
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W. W. M. Pim Pijnappel;
W. W. M. Pim Pijnappel
*Department of Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
†Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands
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Albert J. R. Heck;
Albert J. R. Heck
†Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands
‡Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands
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H. Th. Marc Timmers
H. Th. Marc Timmers
2
*Department of Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands
†Netherlands Proteomics Centre, Padualaan 8, 3584 CH, Utrecht, The Netherlands
2To whom correspondence should be addressed (email h.t.m.timmers@umcutrecht.nl).
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Publisher: Portland Press Ltd
Received:
March 27 2009
Revision Received:
June 15 2009
Accepted:
June 26 2009
Accepted Manuscript online:
June 26 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 422 (3): 443–453.
Article history
Received:
March 27 2009
Revision Received:
June 15 2009
Accepted:
June 26 2009
Accepted Manuscript online:
June 26 2009
Citation
Nga-Chi Lau, Annemieke Kolkman, Frederik M. A. van Schaik, Klaas W. Mulder, W. W. M. Pim Pijnappel, Albert J. R. Heck, H. Th. Marc Timmers; Human Ccr4–Not complexes contain variable deadenylase subunits. Biochem J 15 September 2009; 422 (3): 443–453. doi: https://doi.org/10.1042/BJ20090500
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