Kozak Marilyn
Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Gene. 2005 Nov 21;361:13-37. doi: 10.1016/j.gene.2005.06.037. Epub 2005 Oct 5.
The mechanism of initiation of translation differs between prokaryotes and eukaryotes, and the strategies used for regulation differ accordingly. Translation in prokaryotes is usually regulated by blocking access to the initiation site. This is accomplished via base-paired structures (within the mRNA itself, or between the mRNA and a small trans-acting RNA) or via mRNA-binding proteins. Classic examples of each mechanism are described. The polycistronic structure of mRNAs is an important aspect of translational control in prokaryotes, but polycistronic mRNAs are not usable (and usually not produced) in eukaryotes. Four structural elements in eukaryotic mRNAs are important for regulating translation: (i) the m7G cap; (ii) sequences flanking the AUG start codon; (iii) the position of the AUG codon relative to the 5' end of the mRNA; and (iv) secondary structure within the mRNA leader sequence. The scanning model provides a framework for understanding these effects. The scanning mechanism also explains how small open reading frames near the 5' end of the mRNA can down-regulate translation. This constraint is sometimes abrogated by changing the structure of the mRNA, sometimes with clinical consequences. Examples are described. Some mistaken ideas about regulation of translation that have found their way into textbooks are pointed out and corrected.
原核生物和真核生物的翻译起始机制不同，相应地用于调控的策略也不同。原核生物中的翻译通常通过阻止对起始位点的访问来调控。这是通过碱基配对结构（在mRNA自身内部，或在mRNA与一种小的反式作用RNA之间）或通过mRNA结合蛋白来实现的。每种机制的经典例子都有描述。mRNA的多顺反子结构是原核生物翻译控制的一个重要方面，但多顺反子mRNA在真核生物中不可用（且通常不产生）。真核生物mRNA中的四个结构元件对调控翻译很重要：（i）m7G帽；（ii）AUG起始密码子侧翼的序列；（iii）AUG密码子相对于mRNA 5'端的位置；以及（iv）mRNA前导序列内的二级结构。扫描模型为理解这些效应提供了一个框架。扫描机制还解释了mRNA 5'端附近的小开放阅读框如何下调翻译。这种限制有时会通过改变mRNA的结构而被消除，有时会产生临床后果。文中给出了例子。指出并纠正了一些已进入教科书的关于翻译调控的错误观念。
