Kimura S, Gonzalez F J, Nebert D W
Mol Cell Biol. 1986 May;6(5):1471-7. doi: 10.1128/mcb.6.5.1471-1477.1986.
Expression of the P(1)450 and P(3)450 genes was examined in liver and five extrahepatic tissues of mice after they were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3-methylcholanthrene. All six tissues were shown to have increased P(1)450 and P(3)450 mRNA concentrations after treatment with these inducers. P(3)450 mRNA induction was more sensitive than P(1)450 mRNA induction to small doses of TCDD in liver, kidney, and lung. When transcription run-on assays were compared with mRNA prevalence, control P(3)450 mRNA in liver, kidney, and lung was shown to be 20 to 30 times more stable than control P(1)450 mRNA. After TCDD treatment the increases in mRNA concentrations did not necessarily parallel the increases in transcriptional rate. Thus, the inducer appeared to enhance mRNA stability in some instances. This was evident for liver P(1)450 mRNA, in which an 8-fold rise in transcription was associated with a 27-fold increase in mRNA content, and for kidney P(3)450 mRNA, in which a 2-fold rise in transcription was accompanied by a 12-fold increase in mRNA content. In the kidney and lung of control and TCDD-treated mice, transcriptional rates of the P(3)450 gene were at least 10-fold less than those of the P(1)450 gene. These data indicate that even though both genes are controlled by the same receptor, striking tissue-specific differences in transcription and mRNA stabilization affect the final mRNA concentrations.
在用2,3,7,8-四氯二苯并对二恶英（TCDD）或3-甲基胆蒽处理小鼠后，检测了其肝脏和五种肝外组织中P(1)450和P(3)450基因的表达。在用这些诱导剂处理后，所有六种组织中的P(1)450和P(3)450 mRNA浓度均升高。在肝脏、肾脏和肺中，小剂量TCDD诱导P(3)450 mRNA比诱导P(1)450 mRNA更敏感。当将转录连续分析与mRNA丰度进行比较时，发现肝脏、肾脏和肺中的对照P(3)450 mRNA比对照P(1)450 mRNA稳定20至30倍。TCDD处理后，mRNA浓度的增加不一定与转录速率的增加平行。因此，在某些情况下，诱导剂似乎增强了mRNA的稳定性。这在肝脏P(1)450 mRNA中很明显，其转录增加8倍与mRNA含量增加27倍相关，在肾脏P(3)450 mRNA中也很明显，其转录增加2倍伴随着mRNA含量增加12倍。在对照和TCDD处理小鼠的肾脏和肺中，P(3)450基因的转录速率比P(1)450基因至少低10倍。这些数据表明，尽管这两个基因都由同一受体控制，但转录和mRNA稳定性方面显著的组织特异性差异会影响最终的mRNA浓度。
