Heterogeneous nuclear ribonucleoprotein-A2/B1 modulate collagen prolyl 4-hydroxylase, alpha (I) mRNA stability.
Collagen prolyl 4-hydroxylase (C-P4H) alpha-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-alpha (I) is regulated at the posttrancriptional level under these conditions. Here we report that the induction of C-P4H-alpha (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-alpha (I) mRNA. Luciferase reporter gene assays depending on C-P4H-alpha (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-alpha (I) synthesis under the analyzed conditions. Further indication for the significance of hnRNP-A2/B1 in C-P4H-alpha (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-alpha (I) mRNAs.
Fähling
Michael
M
Charité, Universitätsmedizin Berlin, Institut für Vegetative Physiologie, D-10117 Berlin, Germany. Michael.Faehling@charite.de
Mrowka
Ralf
R
Steege
Andreas
A
Martinka
Peter
P
Persson
Pontus B
PB
Thiele
Bernd J
BJ
D015082:2,2'-Dipyridyl / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000378:metabolism; D005354:Fibrosarcoma / Q000473:pathology; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D006801:Humans; D011393:Procollagen-Proline Dioxygenase / Q000096:biosynthesis* / Q000235:genetics; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000502:physiology*; D014407:Tumor Cells, Cultured
D002614:Chelating Agents; C103749:HNRNPAB protein, human; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D016601:RNA-Binding Proteins; D015082:2,2'-Dipyridyl; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase