AI Article Synopsis
- CYP24 is a vitamin D receptor target gene that is regulated by the active form of vitamin D, 1,25(OH)₂D₃, which increases its expression and also influences its RNA splicing.
- 1,25(OH)₂D₃ was shown to induce specific splicing of the CYP24 RNA in colon cancer cells in a time-dependent manner, suggesting the splicing patterns can vary depending on the cell type or tissue.
- Additionally, the study found that new RNA synthesis is necessary for this splicing and that signaling pathways affect CYP24 splicing, highlighting a dual role for 1,25(OH)₂D₃ in both transcriptional regulation and posttranscriptional modulation of CYP24
Article Abstract
CYP24 is a well-established vitamin D receptor (VDR) target gene. The active VDR ligand 1,25(OH)₂D₃ regulates its own catabolism by increasing CYP24 expression. It is well known that in the presence of 1,25(OH)₂D₃, VDR binds to VDREs in the promoter region of CYP24 and initiates CYP24 transcription. However, little is known about the role of 1,25(OH)₂D₃ in the posttranscriptional modulation of CYP24. In this study, we investigated the functional significance of 1,25(OH)₂D₃ in CYP24 RNA splicing in colon cancer cells. Using RT-PCR, we found that 1,25(OH)₂D₃ actively induces CYP24 splicing in a time-dependent manner and CYP24 splicing pattern could be cell type or tissue specific. The induction of RNA splicing by 1,25(OH)₂D₃ was mainly CYP24 selective. Treatment of cells with parathyroid hormone inhibited basal CYP24 splicing, but failed to inhibit 1,25(OH)₂D₃-induced CYP24 splicing. Further experiments demonstrated that new RNA synthesis was required for the induction of CYP24 splicing by vitamin D. In addition, alteration of multiple signaling pathways also affected CYP24 splicing and cellular sensitivity in response to vitamin D appeared to correlate with the induction of CYP24 splicing. These results suggest that 1,25(OH)₂D₃ not only regulates CYP24 transcription, but also plays an important role in posttranscriptional modulation of CYP24 by inducing its splicing. Our findings reveal an additional regulatory step that makes the vitamin D mediated action more prompt and efficient.
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Article Synopsis
- CYP24 is a vitamin D receptor target gene that is regulated by the active form of vitamin D, 1,25(OH)₂D₃, which increases its expression and also influences its RNA splicing.
- 1,25(OH)₂D₃ was shown to induce specific splicing of the CYP24 RNA in colon cancer cells in a time-dependent manner, suggesting the splicing patterns can vary depending on the cell type or tissue.
- Additionally, the study found that new RNA synthesis is necessary for this splicing and that signaling pathways affect CYP24 splicing, highlighting a dual role for 1,25(OH)₂D₃ in both transcriptional regulation and posttranscriptional modulation of CYP24
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