Heterogeneous nuclear ribonucleoprotein-A2/B1 modulate collagen prolyl 4-hydroxylase, α (I) mRNA stability

Abstract

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. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.