TRAP150在細胞核核醣核酸處理過程的功能探討

Abstract

TRAP150起初被發現為轉錄活化複合體TRAP150/Mediator的一個次單位。此外，TRAP150亦被發現為剪接體的其中一員，說明其可能在訊息核醣核酸剪接中扮演特定的角色。我們最近的報導指出，TRAP150可與其他剪接分子共定位於細胞核內的核斑點中。TRAP150不僅是活體內訊息核醣核酸剪接過程所必須，而其大量表現時，更可大幅活化此剪接過程。我們發現訊息核醣核酸剪接完成之後，TRAP150仍與剪接產物結合，我們亦發現TRAP150可直接與數個exon jounction complex的組成蛋白及運送訊息核醣核酸出核的受器TAP進行結合。此觀察指出TRAP150可能具有調控訊息核醣核酸剪接後事件的功能。當TRAP150被束縛在先驅訊息核醣核酸上時，TRAP150可促進剪接完成的訊息核醣核酸的降解。然而，與典型的無意義媒介訊息核醣核酸降解機制不同之處為，TRAP150調控的訊息核醣核酸降解不依賴轉譯，且發生在細胞核中。儘管TRAP150可藉由不同的獨立區塊活化訊息核醣核酸的剪接以及訊息核醣核酸的降解，我們並不清楚此二功能確切的運作機制。最近，透過尋找TRAP150結合蛋白，我們發現數個腺苷酸化相關蛋白質與其結合。因此，TRAP150可能會協調細胞核內核醣核酸處理過程的不同步驟，並且使異常加工的核醣核酸降解。

TRAP150 was initially identified as a subunit of the transcription coactivator TRAP/Mediator complex. In addition, TRAP150 has also been detected as a component of the spliceosome, suggesting its role in pre-mRNA splicing. We recently reported that TRAP150 colocalizes with splicing factors in nuclear speckles. TRAP150 is not only required for pre-mRNA splicing in vivo, but also substantially activates splicing when overexpressed. We found that TRAP150 remains bound to the spliced mRNA after splicing and accordingly interacts directly with several components of the exon junction complex and the mRNA export receptor TAP. This observation suggests that TRAP150 has a post-splicing function. When tethered to a precursor mRNA, TRAP150 could induce degradation of the spliced mRNA. However, in contrast to the canonical nonsense-mediated decay, TRAP150-mediated mRNA decay is translation independent and occurs in the nucleus. TRAP150 activates pre-mRNA splicing and mRNA degradation via distinct domains, but how it exactly acts in these two events is not yet clear. We recently screened for TRAP150-interacting proteins and found that TRAP150 also associated with polyadenylation factors. Therefore, TRAP150 may function in coordinating different steps of nuclear mRNA processing and perhaps target aberrantly processed mRNAs for degradation.