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

详细信息    查看全文

• 作者：Shannon L. Nowotarski ; Sofia Origanti ; Suzanne Sass-Kuhn ; Lisa M. Shantz
• 关键词：Ornithine decarboxylase ; Tristetraprolin ; Post ; transcriptional regulation ; mRNA stability
• 刊名：Amino Acids
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：48
• 期：10
• 页码：2303-2311
• 全文大小：646 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Analytical Chemistry
  Biochemical Engineering
  Life Sciences
  Proteomics
  Neurobiology
  
• 出版者：Springer Wien
• ISSN：1438-2199
• 卷排序：48

文摘

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.