Farabaugh P J
Department of Biological Sciences and Program in Molecular and Cell Biology, University of Maryland, Baltimore County 21250, USA.
Prog Nucleic Acid Res Mol Biol. 2000;64:131-70. doi: 10.1016/s0079-6603(00)64004-7.
The ribosome rapidly translates the information in the nucleic sequence of mRNA into the amino acid sequence of proteins. As with any biological process, translation is not completely accurate; it must compromise the antagonistic demands of increased speed and greater accuracy. Yet, reading-frame errors are especially infrequent, occurring at least 10 times less frequently than other errors. How do ribosomes maintain the reading frame so faithfully? Geneticists have addressed this question by identifying suppressors that increase error frequency. Most familiar are the frameshift suppressor tRNAs, though other suppressors include mutant forms of rRNA, ribosomal proteins, or translation factors. Certain mRNA sequences can also program frameshifting by normal ribosomes. The models of suppression and programmed frameshifting describe apparently quite different mechanisms. Contemporary work has questioned the long-accepted model for frameshift suppression by mutant tRNAs, and a unified explanation has been proposed for both phenomena. The Quadruplet Translocation Model proposes that suppressor tRNAs cause frameshifting by recognizing an expanded mRNA codon. The new data are inconsistent with this model for some tRNAs, implying the model may be invalid for all. A new model for frameshift suppression involves slippage caused by a weak, near-cognate codon.anticodon interaction. This strongly resembles the mechanism of +1 programmed frameshifting. This may mean that infrequent frameshift errors by normal ribosomes may result from two successive errors: misreading by a near-cognate tRNA, which causes a subsequent shift in reading frame. Ribosomes may avoid phenotypically serious frame errors by restricting apparently innocuous errors of sense.
核糖体迅速将信使核糖核酸（mRNA）核酸序列中的信息转化为蛋白质的氨基酸序列。与任何生物过程一样，翻译并非完全准确；它必须在提高速度和提高准确性这两种相互矛盾的需求之间进行权衡。然而，阅读框错误尤其罕见，其发生频率至少比其他错误低10倍。核糖体是如何如此忠实地维持阅读框的呢？遗传学家通过鉴定增加错误频率的抑制因子来解决这个问题。最常见的是移码抑制tRNA，不过其他抑制因子包括核糖体RNA（rRNA）、核糖体蛋白或翻译因子的突变形式。某些mRNA序列也能使正常核糖体发生移码。抑制和程序性移码的模型描述了明显不同的机制。当代研究对长期以来被接受的突变tRNA导致移码抑制的模型提出了质疑，并为这两种现象提出了一个统一的解释。四重移位模型提出，抑制tRNA通过识别扩展的mRNA密码子导致移码。新数据表明，对于某些tRNA来说，该模型并不适用，这意味着该模型可能对所有情况都无效。一种新的移码抑制模型涉及由弱的、近同源密码子-反密码子相互作用引起的滑动。这与+1程序性移码的机制非常相似。这可能意味着正常核糖体罕见的移码错误可能是由两个连续的错误导致的：近同源tRNA的错读，进而导致阅读框的后续移位。核糖体可能通过限制明显无害的错义错误来避免表型上严重的框错误。
