THE EFFICIENCY OF TRANSLATION TERMINATION IS DETERMINED BY A SYNERGISTIC INTERPLAY BETWEEN UPSTREAM AND DOWNSTREAM SEQUENCES IN SACCHAROMYCES-CEREVISIAE
THE EFFICIENCY OF TRANSLATION TERMINATION IS DETERMINED BY A SYNERGISTIC INTERPLAY BETWEEN UPSTREAM AND DOWNSTREAM SEQUENCES IN SACCHAROMYCES-CEREVISIAE
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DOI：
10.1006/jmbi.1995.0438
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发表时间：
1995-08-18
影响因子：
5.6
通讯作者：
BEDWELL, DM
中科院分区：
文献类型：
--
作者：
BONETTI, B;FU, LW;BEDWELL, DM
在最近的一项研究中，我们发现通过改变酵母停止密码子周围的局部序列上下文，可以使翻译终止的效率降低数百倍。终止抑制被证明是由近同源tRNA与终止密码子错配介导的。我们现在更详细地研究了局部序列上下文如何影响这种生物体中翻译终止的效率。我们的研究结果表明，终止密码子上游的序列在决定翻译终止效率方面起着重要作用。延长的终止序列（包含终止密码子和以下三个核苷酸）也被发现是终止效率的主要决定因素，其影响可归因于第四个核苷酸在很大程度上独立于终止密码子。对于UGA和UAA终止密码子，第4个位置对终止效率（从最有效终止到最低效终止）的影响为G>U，A>C，而对于UAG密码子，其影响为U，A>C>G。这些序列特异性对翻译终止效率的影响表明，多肽链释放因子（或其他可能在翻译终止中起作用的分子，如rRNA）识别了酵母中延长的终止序列。先前的一项研究发现，在一些生物体中，某些四核苷酸序列（包含终止密码子和第一个远端核苷酸）在统计上具有显著的倾向性。我们发现酵母中最常用的四核苷酸序列是介导翻译终止最有效的序列之一，而罕见的四核苷酸序列介导的翻译终止效率要低得多。综上所述，我们的研究结果表明，扩展序列上下文的上游和下游成分协同作用，决定了酵母翻译终止的总体效率。
In a recent study we found that the efficiency of translation termination could be decreased several hundred fold by altering the local sequence context surrounding stop codons in the yeast Saccharomyces cerevisiae. Suppression of termination was shown to be mediated by near-cognate tRNA mispairing with the termination codon. We have now examined in greater detail how the local sequence context affects the efficiency of translation termination in this organism. Our results indicate that the sequence immediately upstream of the termination codon plays a significant role in determining the efficiency of translation termination. An extended termination sequence (containing the stop codon and the following three nucelotides) was also found to be a major determinant of termination efficiency, with effects attributable to the fourth nucleotide being largely independent of the termination codon. For the UGA and UAA stop codons, the influence of the fourth position on termination efficiency (from most efficient to least efficient termination) was found to be G>U,A>C, while for the UAG codon it was U,A>C>G. These sequence-specific effects on the efficiency of translation termination suggest that polypeptide chain release factor (or another molecule that may play a role in translation termination, such as rRNA) recognizes an extended termination sequence in yeast. A previous study found a statistically significant bias toward certain tetranucleotide sequences (containing the stop codon and the first distal nucleotide) in several organisms. We found that tetranucleotide sequences most frequently used in yeast are among the most efficient at mediating translation termination, while rare tetranucleotide sequences mediate much less efficient termination. Taken together, our results indicate that upstream and downstream components of an extended sequence context act synergistically to determine the overall efficiency of translation termination in yeast.