Nuclear import of metallothionein requires its mRNA to be associated with the perinuclear cytoskeleton

M Levadoux, C Mahon, J H Beattie, H M Wallace, J E Hesketh

Research output: Contribution to journalArticle

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Abstract

The influence of mRNA localization on metallothionein-l protein distribution was studied by immunocytochemistry. We used Chinese hamster ovary cells that had been transfected with either a native metallothionein-l gene construct or metallothionein-l 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-l protein, as assessed by radioimmunoassay. The results showed that loss of metallothionein-l mRNA localization was associated with a loss of metallothionein-l protein localization, most notably with a lack of metallothionein-l protein in the nucleus of synchronized cells which were beginning to synthesize DNA This indicates that the association of metallothionein-l mRNA with the cytoskeleton around the nucleus is essential for efficient shuttling of the protein into the nucleus during the G(1) 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.

Original languageEnglish
Pages (from-to)34961-34966
Number of pages6
JournalThe Journal of Biological Chemistry
Volume274
Publication statusPublished - 1999

Keywords

  • MESSENGER-RNA LOCALIZATION
  • BOUND POLYSOMES
  • 3'-UNTRANSLATED REGION
  • PROTEIN-SYNTHESIS
  • RAT HEPATOCYTES
  • C-MYC
  • CYTOPLASM
  • SEQUENCES
  • CELLS
  • LIVER

Cite this

Nuclear import of metallothionein requires its mRNA to be associated with the perinuclear cytoskeleton. / Levadoux, M ; Mahon, C ; Beattie, J H ; Wallace, H M ; Hesketh, J E .

In: The Journal of Biological Chemistry, Vol. 274, 1999, p. 34961-34966.

Research output: Contribution to journalArticle

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abstract = "The influence of mRNA localization on metallothionein-l protein distribution was studied by immunocytochemistry. We used Chinese hamster ovary cells that had been transfected with either a native metallothionein-l gene construct or metallothionein-l 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-l protein, as assessed by radioimmunoassay. The results showed that loss of metallothionein-l mRNA localization was associated with a loss of metallothionein-l protein localization, most notably with a lack of metallothionein-l protein in the nucleus of synchronized cells which were beginning to synthesize DNA This indicates that the association of metallothionein-l mRNA with the cytoskeleton around the nucleus is essential for efficient shuttling of the protein into the nucleus during the G(1) 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.",
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T1 - Nuclear import of metallothionein requires its mRNA to be associated with the perinuclear cytoskeleton

AU - Levadoux, M

AU - Mahon, C

AU - Beattie, J H

AU - Wallace, H M

AU - Hesketh, J E

PY - 1999

Y1 - 1999

N2 - The influence of mRNA localization on metallothionein-l protein distribution was studied by immunocytochemistry. We used Chinese hamster ovary cells that had been transfected with either a native metallothionein-l gene construct or metallothionein-l 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-l protein, as assessed by radioimmunoassay. The results showed that loss of metallothionein-l mRNA localization was associated with a loss of metallothionein-l protein localization, most notably with a lack of metallothionein-l protein in the nucleus of synchronized cells which were beginning to synthesize DNA This indicates that the association of metallothionein-l mRNA with the cytoskeleton around the nucleus is essential for efficient shuttling of the protein into the nucleus during the G(1) 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.

AB - The influence of mRNA localization on metallothionein-l protein distribution was studied by immunocytochemistry. We used Chinese hamster ovary cells that had been transfected with either a native metallothionein-l gene construct or metallothionein-l 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-l protein, as assessed by radioimmunoassay. The results showed that loss of metallothionein-l mRNA localization was associated with a loss of metallothionein-l protein localization, most notably with a lack of metallothionein-l protein in the nucleus of synchronized cells which were beginning to synthesize DNA This indicates that the association of metallothionein-l mRNA with the cytoskeleton around the nucleus is essential for efficient shuttling of the protein into the nucleus during the G(1) 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.

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KW - RAT HEPATOCYTES

KW - C-MYC

KW - CYTOPLASM

KW - SEQUENCES

KW - CELLS

KW - LIVER

M3 - Article

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JO - The Journal of Biological Chemistry

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