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.
authors.affiliation: Division of Science, The Pennsylvania State University Berks Campus, Reading, PA, 19610, USA. sln167@psu.edu.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Nowotarski
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, WI, USA.
authors.forename: Sofia
authors.initials: S
authors.lastname: Origanti
authors.affiliation: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Sass-Kuhn
authors.affiliation: Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Shantz
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D002461:Cell Line, Transformed; D051379:Mice; D018345:Mice, Knockout; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability / Q000502:physiology*; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D051816:Tristetraprolin; C497553:Zfp36 protein, mouse; D009955:Ornithine Decarboxylase
keywords: Ornithine decarboxylase; Post-transcriptional regulation; Tristetraprolin; mRNA stability