轉錄前起始複合體

真核生物mRNA轉錄的轉錄前起始複合體示意圖

轉錄前起始複合體(Transcription preinitiation complex,簡稱PIC)是真核生物古菌細胞基因轉錄前由約100個蛋白質組成的複合體,真核生物轉錄mRNA的前起始複合體包括負責轉錄的RNA聚合酶Ⅱ[1][2]、6種通用轉錄因子TFIIA英语TFIIATFIIB英语TFIIBTFIID英语TFIIDTFIIE英语TFIIETFIIF英语TFIIFTFIIH英语TFIIH)與其他輔助蛋白,組成過程中TFIID的TATA結合蛋白次單元首先在TFIIA的幫助下與DNA啟動子TATA盒(或起始子元件英语initiator element等其他元件)結合[3],接著TFIIB也會與啟動子上的BRE元件(TFIIB-recognition element)結合[4],D、A、B三者與啟動子結合組成的複合體可再吸引TFIIF和RNA聚合酶Ⅱ前來[3],隨後TFIIE、TFIIH再先後與複合體結合[5],後者結合DNA中的模板股,具解旋酶活性,可將啟動子區域的DNA雙股螺旋解開以形成轉錄泡,此外還具激酶活性,可將RNA聚合酶Ⅱ的C端結構域磷酸化以活化聚合酶開始轉錄[5]。除了以上六種通用轉錄因子外,轉錄前起始複合體還包括中介體染色質重塑酶英语Chromatin remodeling、其他共同活化物英语Coactivator (genetics)等調控蛋白[6],其中中介子與轉錄前起始複合體結合後,可與距離較遠的調控序列強化子結合以促進轉錄進行[7]。古菌的轉錄前起始複合體與真核生物的類似,但較為簡化,僅需TATA結合蛋白、TFIIB英语Archaeal transcription factor B與RNA聚合酶,且轉錄因子與DNA結合的方向和真核生物的可能為相反[8]

真核生物的轉錄起始後,聚合酶合成約10個鹼基的RNA時可能發生流产性起始英语abortive initiation,即聚合酶停止轉錄、將此10nt左右的RNA釋出,但仍與啟動子結合,隨後聚合酶成功脫離啟動子和轉錄前起始複合體(啟動子解離)才可繼續轉錄產生完整的mRNA(此過程中RNA聚合酶Ⅱ的C端結構域會被磷酸化[9][10],在此之前可能會發生數次的流产性起始[11]

RNA聚合酶I英语RNA polymerase I(轉錄rRNA)與RNA聚合酶III(轉錄tRNA等小RNA)轉錄起始的機制則與RNA聚合酶II的不同。RNA聚合酶I轉錄前,UBTF先與起始位點上游100至200nt處的上游控制元件(UCE)結合,再與選擇因子I英语Selective factor 1複合體(或稱TIF-IB)結合,促使上游控制元件與啟動子核心區域接觸,隨後RNA聚合酶I再與此複合體結合並開始轉錄[12][13];RNA聚合酶III的轉錄起始則仰賴位於起始位點下游的調控序列(internal control sequences),具體機制因轉錄小RNA的種類而異[14]

參考文獻

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