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核糖体停滞

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维基百科,自由的百科全书
核糖体转译过程示意图

核糖体停滞(Ribosomal pause, Ribosomal stall)[1]是细胞中核糖体转译mRNA时发生停滞的现象,在原核生物真核生物细胞中皆会发生[2][3]核糖体分析英语ribosome profiling等实验技术可用于找出mRNA中发生核糖体停滞的位点[4]

机制

早在1980年代即有研究显示核糖体转译mRNA不同区域的的速率不一致,当时认为转译较慢的位点是因含有罕见的密码子,对应的tRNA在细胞中含量较少,因此与mRNA结合所需的时间较长[5]。但近年核糖体分析的实验结果显示核糖体发生停滞的位点与其对应tRNA的含量不一定有关,意即有些核糖体停滞并非由罕见密码子造成[2]。除此之外造成核糖体停滞的原因还有多脯氨酸序列(polyproline)、tRNA未活化(未连接氨基酸)等[1],此类停滞为可逆,可由eIF5A英语EIF5A(真核生物)或EFP(原核生物)蛋白解决,为细胞调控转译的机制之一,除控制蛋白质转译的产量[6],还可能与蛋白质折叠有关(即在蛋白质的结构域转译结束时发生停滞,让其有时间完成折叠)[7],或者促使核糖体移码发生[8]。缺少eIF5A的真核细胞发生核糖体停滞的频率会增加[9]

有时核糖体停滞为不可逆,原核生物与真核生物皆有将核糖体自mRNA释出的机制。当真核细胞中mRNA上不具终止密码子时,核糖体转译后会停滞于mRNA的末端,此时细胞会启动无终止密码子媒介式分解途径(NSD)将核糖体释出,并将该mRNA与转译的多肽产物降解;有时核糖体会遇到mRNA上较复杂的二级结构而停滞,细胞则可启动转译停滞分解(no-go decay,NGD)途径,亦可将核糖体释出,并降解mRNA及多肽产物[8]。细菌则可以转运-信使RNA(tmRNA)启动反式转译来处理停滞的核糖体[1],部分细菌还有ArfA英语Alternative ribosome-rescue factor AArfB英语Alternative ribosome-rescue factor B等其他途径[1][10]

参考文献

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