2019-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/702334摘要：eIF4G是ㄧ個必需的轉譯起始因子，其作為架橋負責結合eIF4E (Cap-binding protein)、eIF4A (RNA解旋&#37238;)、poly-A結合蛋白和mRNA。從文獻及我們的初步結果中，發現eIF4G在大單元核醣體的生合成亦有功能。核醣體生合成的量和細胞生長速度相關，細胞於對數成長期時，約70%的轉譯及轉錄皆用於生合成核醣體，以支持大量的蛋白質合成需求。核醣體的生合成由核仁開始，於細胞質中結束，其調控嚴謹，過程需要很多個輔助蛋白的參與，若功能有缺失時，會影響核醣體的累積量及功能，進而導致個體的生長及發育缺失，甚至死亡。一些轉譯起始因子亦具有跟核醣體生合成相關的功能，能幫助檢查初生成核醣體重要功能區塊的正確性，只有具有正確構型的核醣體，有能力開始進行轉譯，錯誤的則會進行降解。核醣體生合成的研究有助於抗病毒及抗生素藥物的開發。此外，結果可應用於動植物病理機制的研究。本計劃將以三個目標研究轉譯起始因子eIF4G參與核醣體生合成的角色。目標一將研究eIF4G運送出入核的機制，並研究其出入核的調控和生長、環境間的關係。目標二探討eIF4G參與核醣體生合成的階段及分子功能。目標三將更近一步探討eIF4G參與核醣體生合成的功能區塊，及和60S核醣體結合的位置及型態。這些結果將能知道eIF4G於核醣體生合成的功能及生理上的重要性。<br> Abstract: eIF4G is an essential translation initiation factor. It is a scaffold protein, bridging eIF4E (Cap-binding protein), eIF4A (RNA helicase), PABP (poly-A binding protein) and mRNA. From the previous and our preliminary studies, eIF4G is also shown to have function in 60S biogenesis. In eIF4G&#8710; mutant, the large subunits are under-accumulation. The level of ribosome biogenesis is highly connected with cell growth rate. In the log phase, in order to support abundant protein requirement, about 70% of transcription and translation are used for ribosome synthesis. Ribosome biogenesis starts from the nucleolus and accomplishes in the cytoplasm. More than 200 transacting factors are required for tight regulations of ribosome synthesis. If there is defect in transacting factors, the level and function of ribosome would be impaired, which results in growth retardation, developmental defects, and even death. Some translation factors are also shown to involve in ribosome synthesis. They check integrity of functional domains and allow only correct assembled ones to join translation while the malfunctioned ones will be degraded. Study of ribosome biogenesis helps the developments of antiviral drugs and antibiotics. In addition, the results will be further applied to understand the disease mechanism in plants and animals. This proposal will study the functional role of eIF4G in ribosome synthesis. My experiments outlined in Aim 1 will study the nucleocytoplasmic transport pathway of eIF4G and its regulation in response to growth stage and environmental stimuli. Aim 2 will study at what stage eIF4G joins in 60S biogenesis and its molecular function. Aim 3 will further determine the functional domain(s) of eIF4G and its potential binding site on nascent 60S subunits. Taken together, these data will discover the functional role and physiological importance of eIF4G in 60S biogenesis.核醣體生合成轉譯起始因子出入核調控輔助因子蛋白質合成ribosome biogenesistranslation initiation factortransport regulationtransacting factorsprotein synthesis