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Lookup NU author(s): Dr Marilyne Levadoux, Professor John Hesketh
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The influence of mRNA localization on metallothionein-1 protein distribution was studied by immunocytochemistry. We used Chinese hamster ovary cells that had been transfected with either a native metallothionein-1 gene construct or metallothionein-1 5'-untranslated region and coding sequences linked to the 3'-untranslated region from glutathione peroxidase. The change in the 3'-untranslated region caused the delocalization of the mRNA with a loss of the perinuclear localization and association with the cytoskeleton. Clones were selected which expressed similar levels of metallothionein-1 protein, as assessed by radioimmunoassay. The results showed that loss of metallothionein-1 mRNA localization was associated with a loss of metallothionein-1 protein localization, most notably with a lack of metallothionein-1 protein in the nucleus of synchronized cells which were beginning to synthesize DNA. This indicates that the association of metallothionein-1 mRNA with the cytoskeleton around the nucleus is essential for efficient shuttling of the protein into the nucleus during the G1 to S phase transition. This is the first demonstration of a physiological role for perinuclear mRNA localization and we propose that such localization may be important for a wide range of nuclear proteins, including those that shuttle between nucleus and cytoplasm in a cell cycle dependent manner.
Author(s): Levadoux M, Mahon C, Beattie JH, Wallace HM, Hesketh JE
Publication type: Article
Publication status: Published
Journal: Journal of Biological Chemistry
Year: 1999
Volume: 274
Issue: 49
Pages: 34961-34966
Print publication date: 03/12/1999
ISSN (print): 0021-9258
ISSN (electronic):
Publisher: American Society for Biochemistry and Molecular Biology, Inc.
URL: http://dx.doi.org/10.1074/jbc.274.49.34961
DOI: 10.1074/jbc.274.49.34961
PubMed id: 10574972
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