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研究生(外文):Yu-Cheng Chen
論文名稱(外文):A new RNA Species Located in Human p53 Intron1 Regulates Transcription Level of p53-related Genes
指導教授(外文):Ming-Ta Hsu
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過去一段時間,DNA轉錄為RNA,RNA再轉譯為蛋白質,是分子生物學的主要信條,然而有一些RNA並未攜帶編碼的胺基酸序列,這些RNA除了一些家務基因rRNA、tRNA、snRNA之外,還有一些作為調節性分子的ncRNA(non-coding RNA)。在過去的研究大多以蛋白質的觀點來檢視基因的調控,而最近很多研究報告也指出,這些ncRNA也可能以一些我們未知的機制去調控基因表現,和其他調控因子共同構成細胞內錯綜複雜的調控網絡,以至於我們必須用新的觀點來研究這類RNA,但截至目前為止,並不曉得大部分的ncRNA如何去調控基因表現。
在我們的研究當中,在人類p53的1號內含子發現一段R697序列,在這一段RNA前約一千個序列也具有啟動子活性,而R697的大量表現能使p53 RNA的表現量提昇,但並非透過調控p53啟動子活性,而R697也會調控一些p53相關基因的RNA表現量,更進一步我們發現R697在p53基因敲除的HCT116中,也會調控這些基因的RNA表現量,也就是說R697可以不必透過功能性p53來調節這些p53相關的基因,我們認為R697可能是一段調控基因表現的ncRNA。
In the past, the central dogma is DNA information copied into mRNA, then proteins synthesized using the information in mRNA. However, some RNAs called ncRNA(non-coding RNA) do not encode amino-acid sequence information. Besides the well known house-keeping genes like rRNA, tRNA, snRNA, there are increasing number of regulatory ncRNA molecules being discovered. Regulatory molecules are usually proteins but some study showed ncRNA may regulate gene expression through a number of novel mechanisms, and ncRNA can form complex regulatory framework with other regulatory molecules. However, the regulatory mechanisms of these novel ncRNA are still largely unknown. .
In my study, I discover a new RNA species R697 transcribed within human p53 intron1. This is an polyadenylated RNA of 697 bases. The maximum size of peptide encoded by this small RNA is 37 amino acids. In addition, the 1000bp sequence before R697 in genome have promoter activity. Over-expression of R697 can up-regulate p53 RNA level but not through regulating p53 promoter activity. R697 can also up-regulate the expression of some p53-targeted genes. Furthermore, R697 can up-regulate these genes in HCT116 p53 knock-out cell. This result indicates that R697 regulates these genes independent of functional p53 and suggests that R697 may be a regulatory RNA species that can regulate gene expression.
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