The role of alternative translation start sites in the generation of human protein diversity
The role of alternative translation start sites in the generation of human protein diversity
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DOI：
10.1007/s00438-005-1152-7
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发表时间：
2005-07-01
影响因子：
3.1
通讯作者：
Kolchanov, NA
中科院分区：
文献类型：
--
作者：
Kochetov, AV;Sarai, A;Kolchanov, NA
根据扫描模型，40 S核糖体亚基在它们遇到的第一个（5'近端）AUG密码子处启动翻译。然而，如果第一AUG处于次优上下文中，则其可能无法被识别，并且然后可以在下游AUG处发起翻译。通过这种方式，单个RNA可以产生几种变体产物。早期的实验表明，这些额外的蛋白质变体中的一些可能在功能上很重要。我们已经分析了在5'非翻译区具有AUG三联体的人mRNA和其中注释的翻译起始密码子位于次优环境中的mRNA。结果发现，3%的人类mRNA具有编码注释蛋白的N-末端延伸变体的潜力，12%可以编码N-截短变体。这些蛋白质变体的预测亚细胞定位进行了比较：31%的N-延伸蛋白质和30%的N-截短蛋白质被预测定位到亚细胞区室，这些亚细胞区室不同于注释的蛋白质形式所靶向的亚细胞区室。这些结果表明，额外的AUG可能经常被用于合成具有新功能特性的蛋白质。
According to the scanning model, 40S ribosomal subunits initiate translation at the first (5' proximal) AUG codon they encounter. However, if the first AUG is in a suboptimal context, it may not be recognized, and translation can then initiate at downstream AUG(s). In this way, a single RNA can produce several variant products. Earlier experiments suggested that some of these additional protein variants might be functionally important. We have analysed human mRNAs that have AUG triplets in 5' untranslated regions and mRNAs in which the annotated translational start codon is located in a suboptimal context. It was found that 3% of human mRNAs have the potential to encode N-terminally extended variants of the annotated proteins and 12% could code for N-truncated variants. The predicted subcellular localizations of these protein variants were compared: 31% of the N-extended proteins and 30% of the N-truncated proteins were predicted to localize to subcellular compartments that differed from those targeted by the annotated protein forms. These results suggest that additional AUGs may frequently be exploited for the synthesis of proteins that possess novel functional properties.