Heterogeneous Nuclear Ribonucleoprotein-A2/B1 Modulate Collagen Prolyl 4-Hydroxylase, α (I) mRNA Stability

Collagen prolyl 4-hydroxylase (C-P4H) α-subunit is of regulatory importance in the assembling of C-P4H tetramers, which are necessary for the hydroxylation of procollagen chains. Change in collagen expression by hypoxia or iron diminishment is a significant issue in extracellular matrix remodeling....

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Published in:The Journal of biological chemistry 2006-04, Vol.281 (14), p.9279-9286
Main Authors: Fähling, Michael, Mrowka, Ralf, Steege, Andreas, Martinka, Peter, Persson, Pontus B., Thiele, Bernd J.
Format: Article
Language:English
Subjects:
2,2'-Dipyridyl - pharmacology
Chelating Agents - pharmacology
Collagen - biosynthesis
Enzyme Induction
Extracellular Matrix - metabolism
Fibrosarcoma - pathology
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
Humans
Procollagen-Proline Dioxygenase - biosynthesis
Procollagen-Proline Dioxygenase - genetics
RNA Stability
RNA-Binding Proteins - physiology
Tumor Cells, Cultured
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Summary:Collagen prolyl 4-hydroxylase (C-P4H) α-subunit is of regulatory importance in the assembling of C-P4H tetramers, which are necessary for the hydroxylation of procollagen chains. Change in collagen expression by hypoxia or iron diminishment is a significant issue in extracellular matrix remodeling. It was proposed that C-P4H-α (I) is regulated at the posttrancriptional level under these conditions. Here we report that the induction of C-P4H-α (I) in human fibrosarcoma cells HT1080 by the iron chelator 2,2-dipyridyl is predominantly caused by an enhancement of mRNA stability. This effect is mediated by an increased synthesis and binding of heterogeneous nuclear ribonucleoprotein (hnRNP)-A2/B1, which interacts with a (U)16 element located in the 3′-untranslated region of C-P4H-α (I) mRNA. Luciferase reporter gene assays depending on C-P4H-α (I) 3′-untranslated region and co-transfection with hnRNP-A2/B1 provide evidence that the (U)16 element is necessary and sufficient for posttranscriptional control of C-P4H-α (I) synthesis under the analyzed conditions. Further indication for the significance of hnRNP-A2/B1 in C-P4H-α (I) induction was obtained by micro array experiments. In a data set representing 686 independent physiological conditions, we found a significant positive correlation between hnRNP-A2/B1 and C-P4H-α (I) mRNAs.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M510925200