核糖体停滞

核糖体停滞（Ribosomal pause, Ribosomal stall）^[1]是细胞中核糖体翻译mRNA时发生停滞的现象，在原核生物与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]。

核糖体翻译过程示意图

机制

早在1980年代即有研究显示核糖体翻译mRNA不同区域的的速率不一致，当时认为翻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未激活（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，为细胞调控翻译的机制之一，除控制蛋白质翻译的产量^[6]，还可能与蛋白质折叠有关（即在蛋白质的结构域翻译结束时发生停滞，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，核糖体翻译后会停滞于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与翻译的多肽产物降解；有时核糖体会遇到mRNA上较复杂的二级结构而停滞，细胞则可启动翻译停滞分解（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）启动反式翻译来处理停滞的核糖体^[1]，部分细菌还有ArfA（英语：Alternative ribosome-rescue factor A）、ArfB（英语：Alternative ribosome-rescue factor B）等其他途径^[1][10]。

参考文献

• 分子与细胞生物学主题

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