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啮齿动物下丘脑抗利尿激素基因表达:对生理刺激的转录和转录后反应。

Vasopressin gene expression in the rodent hypothalamus: transcriptional and posttranscriptional responses to physiological stimulation.

作者信息

Murphy D, Carter D

机构信息

Neuropeptide Laboratory, National University of Singapore, Republic of Singapore.

出版信息

Mol Endocrinol. 1990 Jul;4(7):1051-9. doi: 10.1210/mend-4-7-1051.

Abstract

The neuropeptide vasopressin (VP) is expressed in the supraoptic nucleus, a discrete group of neurons in the hypothalamus that respond to osmotic stimuli. In the rat the pattern of expression of VP mRNA changes in two ways as a consequence of the physiological stimulation of these neurons. Firstly, there is an accumulation of VP mRNA, and secondly, the poly(A) tail of the VP mRNA increases in length. We asked whether the increase in VP mRNA level is a consequence of transcriptional or posttranscriptional mechanisms. We present evidence from nuclear run-on assays that increases in the transcription of the rat VP gene are sufficient to account for the accumulation of VP mRNA observed in chronically stimulated animals. However, we note that in acutely stimulated animals there are rapid and relatively large increases in VP gene transcription that do not correlate with increases in the VP mRNA level, but coincide with the appearance of a homogeneous class of VP mRNAs with elongated poly(A) tails. We suggest that immediately after the onset of an acute osmotic stimulus, there is a rapid destruction of preexisting VP mRNAs and their replacement with new transcripts bearing longer poly(A) tails. We have also addressed the question of the function of the elongated VP mRNA poly(A) tail. It is unlikely that the poly(A) tail extension is involved in RNA stability; the transcriptional changes observed are sufficient to account for the increase in VP mRNA level, and we show that in the mouse similar increases in VP mRNA level are observed without concomitant changes in poly(A) tail length. We did not observe a change in the polysome distribution of the VP mRNA after osmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

神经肽血管加压素(VP)在下丘脑视上核中表达,视上核是一组对渗透压刺激有反应的离散神经元。在大鼠中,由于这些神经元的生理刺激,VP mRNA的表达模式以两种方式发生变化。首先,VP mRNA会积累,其次,VP mRNA的聚腺苷酸尾长度增加。我们研究了VP mRNA水平的增加是转录机制还是转录后机制的结果。我们通过核转录分析提供的证据表明,大鼠VP基因转录的增加足以解释在长期受刺激动物中观察到的VP mRNA积累。然而,我们注意到在急性受刺激的动物中,VP基因转录有快速且相对较大的增加,这与VP mRNA水平的增加不相关,但与一类具有延长聚腺苷酸尾的均匀VP mRNA的出现相吻合。我们认为,在急性渗透压刺激开始后,先前存在的VP mRNA会迅速被破坏,并被带有更长聚腺苷酸尾的新转录本所取代。我们还探讨了延长的VP mRNA聚腺苷酸尾的功能问题。聚腺苷酸尾延长不太可能参与RNA稳定性;观察到的转录变化足以解释VP mRNA水平的增加,并且我们表明在小鼠中观察到VP mRNA水平有类似增加,而聚腺苷酸尾长度没有相应变化。我们在渗透压刺激后未观察到VP mRNA的多核糖体分布发生变化。(摘要截短至250字)

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