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標題: | 果蠅去頭蓋蛋白質1的發育遺傳分析 Developmental genetic analysis of Drosophila decapping protein 1, dDcp1 |
作者: | Ming-Der Lin 林明德 |
指導教授: | 周子賓(Tze-Bin Chou) |
關鍵字: | 果蠅,去頭蓋蛋白質1, Drosophila,decapping protein 1,dDcp1, |
出版年 : | 2006 |
學位: | 博士 |
摘要: | 在果蠅卵發育的過程(oogenesis)中,母系訊息核醣核酸(maternal mRNA)在卵母細胞(oocyte)內特定位置的分佈與定位對於胚胎時期的發育扮演非常重要的角色。例如oskar (osk) 訊息核醣核酸在卵母細胞後端的定位決定極細胞(pole cells)與胚胎腹部腹節的形成。
除了輸送osk 訊息核醣核酸到後端的特定蛋白質外,參與訊息核醣核酸剪接(splicing)機制的成員也與osk 訊息核醣核酸的運送過程有關;例如一些Exon junction complex的蛋白質成員被破壞時,osk無法被運送到卵母細胞後端。此外,與蛋白質轉譯起始過程有關的蛋白質亦參與調控osk的運送;例如 eIF4E以及其他相關的轉譯起始調控因子都與osk 在卵母細胞後端的定位有關。 在特定之輸送機制、剪接機制與轉譯機制外,訊息核醣核酸的裂解(degradation)機制是否也參與osk 訊息核醣核酸在卵母細胞後端的定位並未被報導。本論文主要在說明果蠅的訊息核醣核酸裂解系統中的去頭蓋蛋白質1 (Drosophila decapping protein 1, dDcp1) 不但參與母系訊息核醣核酸在胚胎時期的裂解並且也是osk訊息核醣核酸輸送複合體的成員。本論文證實果蠅去頭蓋蛋白質1為輸送 osk往卵母細胞後端運送的過程所需,並揭示其參與並調控此運送過程的機制與其在卵發育過程中所扮演的其他可能角色。 在酵母菌與人類細胞中,訊息核醣核酸的裂解被發現坐落於細胞質中稱為Processing bodies (P-bodies)的特殊構造。P-bodies 的構造中包含了去頭蓋蛋白質1(Dcp1)、去頭蓋蛋白質2 (Dcp2)與5’ 往 3’ 外切核醣核酸酵素(5’ to 3’ exoribonuclease;Xrn1) 以及其它參與5’ 往3’ 之訊息核醣核酸裂解所需的相關蛋白質。在卵母細胞中去頭蓋蛋白質1坐落於卵母細胞的後端,其在卵母細胞後端的分佈狀態乃由osk 訊息核醣核酸所在之位置以及含量所決定。在護理細胞(nurse cells)中,去頭蓋蛋白質1分佈於細胞質並與去頭蓋蛋白質2、果蠅5’ 往 3’ 外切核醣核酸酵素(Pacman) 以及 Me31B 等蛋白質形成點狀的構造。本論文證實這些點狀構造就是果蠅護理細胞中參與訊息核醣核酸裂解的P-bodies。 人類去頭蓋蛋白質1的同源蛋白質,hDcp1a,也被發現為參與傳遞TGF-beta訊息路徑的轉錄激活因子(transactivation factor)並且被命名為SMIF (Smad4-Interacting Factor)。果蠅去頭蓋蛋白質1除了參與osk在卵母細胞後端的運送外,本論文並證實去頭蓋蛋白質1的N端會與Medea蛋白質(Drosophila Smad4)的MH1區域進行交互作用,而且其蛋白質的C端在酵母菌裡有激活基因轉錄活性的能力。唯,果蠅去頭蓋蛋白質1參與TGF-beta訊息傳遞路徑在卵的發育過程中所扮演的角色仍然需要進一步的實驗與分析。 Specific subcellular localization of maternal mRNAs in the oocyte during oogenesis is very important for proper embryonic patterning in Drosophila. For example, the deposition of oskar (osk) mRNA at the posterior pole of the oocyte is critical for both pole cells and abdomen formation. Many mechanisms are involved in the posterior deposition of osk mRNA. In addition to those directly involved in the osk mRNA transportation, proteins participate in pre-mRNA splicing, such as Exon junction complex components, are implicated in osk mRNA transportation. Moreover, proteins that participate in mRNA translation, such as eIF4E and others related to translational initiation, can direct the posterior transportation of osk mRNA. Except for the transportation, splicing, and translation machineries, the mRNA degradation machinery has not been reported to participate in the regulation of osk mRNA transport. Evidence presented here indicates that Drosophila decapping protein 1 (dDcp1) is required for not only the maternal mRNA degradation during early embryogenesis but also the posterior transportation of osk mRNA. As a component of osk mRNP complex, the mechanism of dDcp1-directed osk mRNA transportation and the possible roles of dDcp1 during oogenesis are discussed. In both yeast and human cells, the sites of 5’ to 3’ mRNA degradation have been found to reside in specific cytoplasmic foci, named Processing bodies (P-bodies). P-bodies contain Decapping protein 1 (Dcp1), Decapping protein 2 (Dcp2), 5’ to 3’ exoribonuclease (Xrn1), and other proteins required for 5’ to 3’ mRNA degradation. In the oocyte, dDcp1 is localized at the posterior end and its localization is osk mRNA dosage- and position-dependent. In nurse cell cytoplasm, dDcp1 is localized in the cytosol and is colocalized with dDcp2, Drosophila 5’ to 3’ exoribonuclease (Pacman), and Me31B in discrete cytoplasmic foci. Evidence provided here indicates that these cytoplasmic dDcp1 bodies in nurse cells are Drosophila P-bodies. The human homolog of Dcp1, hDcp1a, has been found to involve in the TGF-beta signaling pathway and is also named as SMIF (Smad4-interacting factor). In addition to the requirement of dDcp1 for the posterior transport of osk mRNA, the N-terminal of dDcp1 can interact with the MH1 domain of Medea (Drosophila Smad4 homolog). Besides, dDcp1 contains intrinsic transactivation activity in its C-terminal region and is able to translocate into the nucleus in response to the Dpp signaling. However, the possible roles of dDcp1 in the TGF-beta signaling during oogenesis remain to be clarified. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33698 |
全文授權: | 有償授權 |
顯示於系所單位: | 分子與細胞生物學研究所 |
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