Heterogeneous nuclear ribonucleoprotein-A2/B1 modulate collagen prolyl 4-hydroxylase, α(I) mRNA stability
Heterogeneous nuclear ribonucleoprotein-A2/B1 modulate collagen prolyl 4-hydroxylase, α(I) mRNA stability
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DOI：
10.1074/jbc.m510925200
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发表时间：
2006-04-07
影响因子：
4.8
通讯作者：
Thiele, BJ
中科院分区：
文献类型：
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作者：
Fähling, M;Mrowka, R;Thiele, BJ
胶原蛋白脯氨酰4-羟化酶（C-P4 H）α亚基在C-P4 H四聚体的组装中具有重要的调节作用，C-P4 H四聚体是前胶原链羟基化所必需的。缺氧或铁减少引起的胶原蛋白表达变化是细胞外基质重塑的重要问题。有人提出，在这些条件下，C-P4 H-alpha（I）在转录后水平受到调节。在这里，我们报告的诱导C-P4 H-α（I）在人纤维肉瘤细胞HT 1080的铁螯合剂2，2-联吡啶主要是由于mRNA的稳定性增强。这种效应是由异质核核糖核蛋白（hnRNP）-A2/B1的合成和结合增加介导的，hnRNP-A2/B1与位于C-P4 H-α（I）mRNA 3 '非翻译区的（U）16元件相互作用。根据C-P4 H-alpha（I）3 '-非翻译区和与hnRNP-A2/B1共转染的荧光素酶报告基因测定提供了证据，证明（U）16元件对于在分析条件下C-P4 H-alpha（I）合成的转录后控制是必要的和充分的。通过微阵列实验获得hnRNP-A2/B1在C-P4 H-α（I）诱导中的显著性的进一步指示。在代表686个独立生理条件的数据集中，我们发现hnRNP-A2/B1和C-P4 H-alpha（I）mRNA之间存在显著的正相关性。
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.