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ANALYSIS OF BIOLOGICAL ROLE OD ANTISENSE RNA ON REGULATION OF GENE EXPRESSION

OD反义RNA对基因表达调控的生物学作用分析

基本信息

批准号：
05454441
负责人：
KATO Junzo
金额：
$ 4.29万
依托单位：
YAMANASHI MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454441/
关键词：
GnRH antisense RNA rat hypothalamus brain GnRH mRNA アンチセンス SH-RNAs アンチセンスSH RNA GnRH analogue

项目摘要

The aim of the research project is analysis of the presense and biological role of the GnRH antisense RNAs in the rat hypothalamus and the other brain regions. In order to clarify the role, we have established the sensitive- and specific assay for detection of the GnRH antisense RNAs. Using this assay, we firstly demonstrated the presence of the GnRH antisense RNAs in the rat the brain regions including the hypothalamus. Since the ratio of the level of the GnRH antisense RNAs to the GnRH sense mRNA was higher in the brain regions other than the hypothalamus, it was implied that the GnRH antisense RNAs might suppress the gene expression of the GnRH in these region. Furthermore, the changes in the levels of the GnRH antisense RNAs and GnRH mRNA in the hypothalamus were studied in the GnRH analogue-treated rats. The level of the GnRH antisense RNAs increased after the administration of the GnRH analogue, and thereafter decreased. On the other hand, the level of the GnRH mRNA decreased after the GnRH analogue-treatment, and then increased. These results inferred that the gene expression of the GnRH might be regulated, at least in part, by the GnRH antisense RNAs in the hypothalamus.In conclusion, it is indicated that the GnRH antisense RNAs may play some important role in the regulation of the GnRH gene expression. However, it remains to be elucidated that the regulatory mechanism of the transcription of the GnRH antisense RNAs. Now we are addressing these subjects to investigate the possibility of the clinical application of the antisense RNAs.

该研究项目的目的是分析 GnRH 反义 RNA 在大鼠下丘脑和其他大脑区域的存在和生物学作用。为了阐明其作用，我们建立了灵敏且特异的 GnRH 反义 RNA 检测方法。使用该测定，我们首先证明了大鼠大脑区域（包括下丘脑）中存在 GnRH 反义 RNA。由于GnRH反义RNA与GnRH有义mRNA水平的比率在下丘脑以外的脑区域中较高，因此暗示GnRH反义RNA可能抑制这些区域中GnRH的基因表达。此外，在GnRH类似物治疗的大鼠中研究了下丘脑中GnRH反义RNA和GnRH mRNA水平的变化。 GnRH反义RNA的水平在施用GnRH类似物后增加，然后降低。另一方面，GnRH mRNA的水平在GnRH类似物处理后降低，然后升高。这些结果推断，GnRH基因表达可能至少部分受到下丘脑中GnRH反义RNA的调节。综上所述，表明GnRH反义RNA可能在GnRH基因表达的调节中发挥重要作用。然而，GnRH反义RNA的转录调控机制仍有待阐明。现在我们正在针对这些课题来研究反义RNA临床应用的可能性。