短散在核元件

反轉錄轉座子序列

短散在核元件(Short interspersed nuclear elements,簡稱SINE)是真核生物基因組中長100至700bp的轉位子序列[1],屬於反轉錄轉座子,哺乳類基因組約有13%為SINE[2]。SINE與LINE等轉位子皆是「寄生」於生物基因組中的DNA元件,某些情況下可能對生物體有害,但有時細胞也將其用來調控自己的基因表現[3]

人類與小鼠基因組中的LINE1與SINE

SINE一般不具有長末端重複序列(LTR)[4],其序列從5端至3端可大致分為頭端、中端與尾端三部分,其中頭端大多來自tRNA等由RNA聚合酶III轉錄的RNA[5],例如Alu元件的5端序列即來自7SL RNA[6];中端序列常與長散在核元件(LINE)相似,因此可利用後者編碼的內切酶;尾端則是由一些重複序列組成[7]

SINE頭端的序列與tRNA等小RNA相似,可被RNA聚合酶III轉錄[8],且其啟動子和tRNA一樣是轉錄序列的一部份(稱為「內部啟動子」),而非位於其上游[9]。SINE轉錄出的mRNA不編碼任何蛋白質,相較之下LINE可編碼具內切酶和反轉錄酶活性的蛋白,SINE因具有和LINE同源的序列[10],其RNA跟LINE的RNA均可利用這些蛋白,反轉錄成DNA後再隨機插入基因組中[4][11]。SINE因需仰賴基因組中的其他序列編碼的酵素才能增殖,屬於非自主的逆轉錄轉座子(non-autonomous retrotransposon),而LINE則是自主的逆轉錄轉座子(autonomous retrotransposon)[12]。LINE的轉錄在生殖系細胞英語Germline cells和早期胚胎中較為活躍,因此SINE也大多在這些階段轉錄增殖,胚胎發育後期以後,體細胞中SINE的轉錄一般會被抑制,不過某些狀況下可能使其恢復表現[13]

Alu元件靈長類演化過程中相當重要的SINE,約長300bp,人類基因組中有超過百萬個Alu元件,占基因組大小超過10%[14],許多其他動物基因組中也有大量的SINE[15]。SINE插入重要的基因序列可影響基因表現而造成人類的遺傳疾病[13][16] ,例如有些乳癌大腸癌白血病血友病囊腫性纖維化神經纖維瘤病Dent病英語Dent's disease為Alu元件插入造成[4]

參考文獻

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