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強化子RNA

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強化子RNA可能的作用機制

強化子RNA(Enhancer RNA,簡稱eRNA)是真核生物基因組強化子序列轉錄產生的非編碼RNA[1],長50nt至4000nt之間,此類RNA於2010年由RNA測序ChIP-seq等大規模測序技術測得[2]。強化子為基因組中與RNA聚合酶Ⅱ中介體轉錄因子結合以啟動基因轉錄的重要序列,其轉錄生成的強化子RNA大多留在細胞核中,此類RNA大多不穩定,易被細胞核中的外切體降解,但可能可調控其他基因的轉錄[3]。並非所有強化子皆可轉錄,有研究顯示僅有少數強化子可轉錄產生出eRNA[4],可能為較為活躍的強化子[5]。有些強化子RNA具複雜的次級結構,並帶有m6A等鹼基修飾[5]

強化子RNA可分為1D eRNA與2D eRNA兩大類,兩者長度、多腺苷酸化情況與轉錄方向皆有差異[6],1D eRNA的轉錄為單向,長度可達數千nt,較常被多腺苷酸化[5],一般由H3K4me1英語H3K4me1/H3K4me3英語H3K4me3比值較低的強化子轉錄[7];2D eRNA的轉錄則為雙向,且長度較短,介於50nt至2000nt之間,轉錄的強化子H3K4me1/H3K4me3較高[8]

有研究認為強化子RNA僅是基因轉錄的中的雜訊,即由染色體結構疏鬆的區域所隨機轉錄產生、不具重要功能的RNA[4][9][10],但有許多研究認為強化子RNA可能具重要的轉錄調控功能,可影響特定基因的表現,其詳細機制尚不明朗,但目前已有數個假說被提出[6],有些強化子RNA可能可和組蛋白修飾酶轉錄因子等調控蛋白結合,以促進該強化子所控制基因的轉錄,例如周期蛋白D1基因強化子轉錄出的eRNA可結合組蛋白乙醯轉移酶以促進周期蛋白D1的轉錄[3],受p53調控的各目標基因之強化子p53BER也可轉錄出eRNA以促進各目標基因轉錄[11];還有些強化子RNA可能可調控其他較遠位點的基因的轉錄[12]。有eRNA可能可作為一些癌症病理狀況的生物標記[5][13]

參考文獻

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