Heterogeneous nuclear ribonucleoprotein (hnRNP) C plays a key role in RNA processing. More recently hnRNP C has also been shown to function as a DNA binding protein exerting a dominant-negative effect on transcriptional responses to the vitamin D hormone,1,25-dihydroxyvitamin D (1,25(OH)2D), via interaction in cis with vitamin D response elements (VDREs). The physiologically active form of human hnRNPC is a tetramer of hnRNPC1 (huC1) and C2 (huC2) subunits known to be critical for specific RNA binding activity in vivo, yet the requirement for heterodimerization of huC1 and C2 in DNA binding and downstream action is not well understood. While over-expression of either huC1 or huC2 alone in mouse osteoblastic cells did not suppress 1,25(OH)2D-induced transcription, over-expression of huC1 and huC2 in combination using a bone-specific polycistronic vector successfully suppressed 1,25(OH)2D-mediated induction of osteoblast target gene expression. Over-expression of either huC1 or huC2 in human osteoblasts was sufficient to confer suppression of 1,25(OH)2D-mediated transcription, indicating the ability of transfected huC1 and huC2 to successfully engage as heterodimerization partners with endogenously expressed huC1 and huC2. The failure of the chimeric combination of mouse and human hnRNPCs to impair 1,25(OH)2D-driven gene expression in mouse cells was structurally predicted, owing to the absence of the last helix in the leucine zipper (LZ) heterodimerization domain of hnRNPC gene product in lower species, including the mouse. These results confirm that species-specific heterodimerization of hnRNPC1 and hnRNPC2 is a necessary prerequisite for DNA binding and down-regulation of 1,25(OH)2D-VDR-VDRE-directed gene transactivation in osteoblasts.

中文翻译：

---

异质核糖核蛋白C1 / C2的异二聚体结构决定了成骨细胞中1,25-二羟基维生素D定向转录事件。

异核核糖核蛋白（hnRNP）C在RNA加工中起关键作用。最近，hnRNP C还被证明可作为DNA结合蛋白，通过顺式相互作用对维生素D激素1,25-二羟基维生素D（1,25（OH）2D）的转录反应发挥显性负作用。含有维生素D反应元素（VDRE）。人hnRNPC的生理活性形式是hnRNPC1（huC1）和C2（huC2）亚基的四聚体，已知对体内特定RNA结合活性至关重要，但对huC1和C2在DNA结合和下游作用中异源二聚化的要求并非如此非常明白。虽然在小鼠成骨细胞中单独表达huC1或hu​​C2并不能抑制1,25（OH）2D诱导的转录，联合使用骨特异性多顺反子载体的huC1和huC2的过表达成功抑制了1,25（OH）2D介导的成骨细胞靶基因表达诱导。huC1或hu​​C2在人类成骨细胞中的过度表达足以赋予1,25（OH）2D介导的转录抑制作用，表明转染的huC1和huC2成功地与内源表达的huC1和huC2成为异源二聚体。结构上预测了小鼠和人类hnRNPC的嵌合组合破坏小鼠细胞中1,25（OH）2D驱动的基因表达的失败，因为hnRNPC的亮氨酸拉链（LZ）异二聚结构域中没有最后一个螺旋低等物种的基因产物，包括小鼠。