2014-01-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/698250摘要：在生物體中，蛋白質並不都是均質的分佈在細胞質中，有些蛋白必需在特定的細胞部位合成，來專一調控細胞的生理機制，比如胚胎及神經元細胞突觸的分化等。為了控制蛋白質只在特定的地方合成，mRNA一被轉錄出來後，特定蛋白質會先鍵結在上面來抑制轉譯的進行；當mRNA被送到該表現的地方後，這些抑制轉譯的蛋白會離開，使mRNA的訊息得以表現。在酵母菌中，Ash1是控制matting type 改變的蛋白質，ASH1 mRNA 在母細胞合成後，會被送往子細胞的胞尖 (bud tip)，進行表現，因此，常被來用來作為mRNA不對稱分布研究的模式。Puf6能辨認mRNA 3端的非轉譯序列，來進一步鍵結並抑制ASH1 mRNA的表現，因此在puf6△的細胞中，Ash1會分布在母細胞及子細胞中。除此之外，Puf6也被發現和核醣體生合成相關，但是，Puf6的角色、及詳細的調控機制，至今仍不清楚。核醣體生合成是一個耗能且複雜的步驟，若合成出問題時，會造成細胞活性下降甚至死亡。在puf6△的細胞，大核醣體的合成下降，且累積在細胞核中，表示其生合成途徑出問題；因此，此研究將著重於探討Puf6在核醣體生合成中的功能，及其如何能在細胞中調控兩種不同的功能；再進一步的探討，這兩條重要的生理途徑間，可能存在的重要調控機制。<br> Abstract: Asymmetric protein localization is important in regulation of cellular functions. In order to control the protein expression at specific area, the cells have different ways to accomplish it. One main strategy is to transport the mRNAs along with proteins which can suppress its translation to the expression site. After the proteins leave from this compartment, mRNAs are then freely exposed to the translation machineries for the biological function. Puf6 was identified as an important factor in ASH1 mRNA local distribution. Ash1 is only expressed at the bud tips of the daughter cells in wild type while it is distributed evenly in both mother and daughter cells in puf6△ mutant. Recently, Puf6 was also identified as a 60S biogenesis factor in yeast. The synthesis of 60S was decreased and blocked in the nucleus in puf6△ cells. However, the detailed mechanism how Puf6 regulate ribosome biogenesis pathway is still unclear. The synthesis of ribosome is a multiple-step process from nucleolus to cytoplasm and an intense energy cost pathway. It is tightly regulated based on the cell cycle and nutrition status. At present less attention was paid on this protein at the functional role of ribosome biogenesis. The present work will result in establishment of this protein and would like to address the functional role of Puf6 in the synthesis of large ribosomal subunits, and how it regulates these two important pathways. Furthermore, we would explore the potential links between these two pathways and the physiological importance will definitely in future going to address at several areas of research.核醣體核醣體生合成蛋白質不對稱分布轉譯調控區域mRNAmRNA distribution (localized mRNA)translational controlribosome biogenesisPuf6asymmetric protein distribution