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

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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.