第九纖維母細胞生長因子(FGF9)為一種自體分泌及旁分泌的生長因子，並且在胚胎、器官、性別發育與正常生理機制的維持上扮演重要的角色。進一步說，FGF9的基因表現量對生命至關重要。FGF9之異常表現被發現與許多疾病有關連性，暗示著FGF9在不同的表現量、組織、及時間需要被精密的控制。因此，瞭解細胞如何調控FGF9的表現對探討其在病理上所扮演之角色是一項重要的議題。這份報告主要著重在研究FGF9三端未轉譯區(3’UTR)是否參與在其基因調控的機制中。藉由在二十一位性別倒置的病人與七十二位正常人對FGF9基因做系統性搜索，發現一個位在FGF9 3’UTR的微衛星，TG雙核酸重複序列，與人類性腺發育缺失有相關性存在。深入探討更證實此TG重複序列可以在前、後轉錄層次調控基因表現量。此外，我們也在FGF9 3’UTR發現一個具有演化保留性的序列，AU-rich element (ARE)，並證實藉由AU-rich element binding protein 1 (AUF1)的結合而對FGF9核醣核酸(mRNA)的穩定性產生重大影響。最後，我們證實透過AUF1參與的mRNA快速降解可以控制FGF9表現量的恆定。而本報告證實了3’UTR對FGF9表現的重大影響力，進而對FGF9相關生理反應扮演極重要的角色。

Fibroblast growth factor 9 (FGF9) is an autocrine/paracrine growth factor that plays critical roles in embryonic and organic development, sexual determination and diverse physiologic events. FGF9 mRNA is ubiquitously expressed in embryonic stage but is restricted to adult brain and kidney. Aberrant expression of FGF9 is associated with several pathological conditions, suggesting that the level, tissues, and stages of FGF9 expression need to be precisely controlled. This report is fuscous on investigating whether the 3’ untranslated region (3’UTR) of the human FGF9 is involved in FGF9 gene regulation. Systematical screening of FGF9 gene in 21 XY females and 72 XX females and XY males shows that a polymorphic microsatellite (MS) motif, the TG dinucleotide repeat, is located at FGF9 3’UTR and associated with human gonadal dysgenesis. Further experiments demonstrated that the (TG)n motif modulated gene expression at both pre- and post-transcriptional levels. In addition, we also identified an evolutionary conserved AU-rich element (ARE) in FGF9 3’UTR and demonstrated it is crucial for FGF9 mRNA stability through the interaction with AU-rich element binding protein 1 (AUF1). Finally, we showed that AUF1 medicated FGF9 rapid degradation controls the homeostasis of FGF9 expression, which in turns to play a critical role in the FGF9-medicated biological processes.

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