Destabilization of the ornithine decarboxylase mRNA transcript by the RNA-binding protein tristetraprolin

Shannon Lyn Nowotarski, Sofia Origanti, Suzanne Sass-Kuhn, Lisa Shantz

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. In a normal physiological state, ODC is tightly regulated. However, during neoplastic transformation, ODC expression becomes upregulated. The studies described here show that the ODC mRNA transcript is destabilized by the RNA-binding protein tristetraprolin (TTP). We show that TTP is able to bind to the ODC mRNA transcript in both non-transformed RIE-1 cells and transformed Ras12V cells. Moreover, using mouse embryonic fibroblast cell lines that are devoid of a functional TTP protein, we demonstrate that in the absence of TTP both ODC mRNA stability and ODC enzyme activity increase when compared to wild-type cells. Finally, we show that the ODC 3′ untranslated region contains cis acting destabilizing elements that are affected by, but not solely dependent on, TTP expression. Together, these data support the hypothesis that TTP plays a role in the post-transcriptional regulation of the ODC mRNA transcript.

Original languageEnglish (US)
Pages (from-to)2303-2311
Number of pages9
JournalAmino Acids
Volume48
Issue number10
DOIs
StatePublished - Oct 1 2016

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Tristetraprolin
Ornithine Decarboxylase
RNA-Binding Proteins
Messenger RNA
Biosynthetic Pathways
Reactive ion etching
RNA Stability
Polyamines
Enzyme activity
3' Untranslated Regions
Enzymes
Fibroblasts

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

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title = "Destabilization of the ornithine decarboxylase mRNA transcript by the RNA-binding protein tristetraprolin",
abstract = "Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. In a normal physiological state, ODC is tightly regulated. However, during neoplastic transformation, ODC expression becomes upregulated. The studies described here show that the ODC mRNA transcript is destabilized by the RNA-binding protein tristetraprolin (TTP). We show that TTP is able to bind to the ODC mRNA transcript in both non-transformed RIE-1 cells and transformed Ras12V cells. Moreover, using mouse embryonic fibroblast cell lines that are devoid of a functional TTP protein, we demonstrate that in the absence of TTP both ODC mRNA stability and ODC enzyme activity increase when compared to wild-type cells. Finally, we show that the ODC 3′ untranslated region contains cis acting destabilizing elements that are affected by, but not solely dependent on, TTP expression. Together, these data support the hypothesis that TTP plays a role in the post-transcriptional regulation of the ODC mRNA transcript.",
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Destabilization of the ornithine decarboxylase mRNA transcript by the RNA-binding protein tristetraprolin. / Nowotarski, Shannon Lyn; Origanti, Sofia; Sass-Kuhn, Suzanne; Shantz, Lisa.

In: Amino Acids, Vol. 48, No. 10, 01.10.2016, p. 2303-2311.

Research output: Contribution to journalArticle

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T1 - Destabilization of the ornithine decarboxylase mRNA transcript by the RNA-binding protein tristetraprolin

AU - Nowotarski, Shannon Lyn

AU - Origanti, Sofia

AU - Sass-Kuhn, Suzanne

AU - Shantz, Lisa

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N2 - Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. In a normal physiological state, ODC is tightly regulated. However, during neoplastic transformation, ODC expression becomes upregulated. The studies described here show that the ODC mRNA transcript is destabilized by the RNA-binding protein tristetraprolin (TTP). We show that TTP is able to bind to the ODC mRNA transcript in both non-transformed RIE-1 cells and transformed Ras12V cells. Moreover, using mouse embryonic fibroblast cell lines that are devoid of a functional TTP protein, we demonstrate that in the absence of TTP both ODC mRNA stability and ODC enzyme activity increase when compared to wild-type cells. Finally, we show that the ODC 3′ untranslated region contains cis acting destabilizing elements that are affected by, but not solely dependent on, TTP expression. Together, these data support the hypothesis that TTP plays a role in the post-transcriptional regulation of the ODC mRNA transcript.

AB - Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. In a normal physiological state, ODC is tightly regulated. However, during neoplastic transformation, ODC expression becomes upregulated. The studies described here show that the ODC mRNA transcript is destabilized by the RNA-binding protein tristetraprolin (TTP). We show that TTP is able to bind to the ODC mRNA transcript in both non-transformed RIE-1 cells and transformed Ras12V cells. Moreover, using mouse embryonic fibroblast cell lines that are devoid of a functional TTP protein, we demonstrate that in the absence of TTP both ODC mRNA stability and ODC enzyme activity increase when compared to wild-type cells. Finally, we show that the ODC 3′ untranslated region contains cis acting destabilizing elements that are affected by, but not solely dependent on, TTP expression. Together, these data support the hypothesis that TTP plays a role in the post-transcriptional regulation of the ODC mRNA transcript.

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