Evolutionary conservation suggests a regulatory function of AUG triplets in 5'-UTRs of eukaryotic genes.
Evolutionary conservation suggests a regulatory function of AUG triplets in 5'-UTRs of eukaryotic genes.
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DOI：
10.1093/nar/gki847
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发表时间：
2005
影响因子：
14.9
通讯作者：
Koonin EV
中科院分区：
文献类型：
--
作者：
Churbanov A;Rogozin IB;Babenko VN;Ali H;Koonin EV
通过比较人、小鼠和大鼠的正向同源基因序列，我们发现在哺乳动物cDNA的5′-非翻译区（5′-UTR），而不是3′-UTR或编码序列中，AUG比其他63 nt三联体中的任何一个都保守得多。这种效应可能主要反映了真正的进化保守性，而不是cDNA注释伪像，因为在含有终止密码子的5′-UTR中观察到过量的保守上游AUG（uAUG）与起始AUG符合读框，并且许多保守AUG位于不同的读框中，与真实非编码序列中的位置一致。总之，保守的uAUG存在于至少20-30%的哺乳动物基因中。通过比较来自酵母属的不同种的正向同源基因，获得了定性相似的结果。结合哺乳动物和酵母5′-UTR中AUG总含量显著减少的观察结果，这些发现表明5′-UTR中的AUG三联体受到两个相反方向的纯化选择压力：没有特定功能的uAUG往往是有害的，并在进化过程中被淘汰，而那些具有功能的uAUG是保守的。最有可能的是，保守的uAUG的主要作用是在起始阶段减弱翻译，这通常另外由哺乳动物5′-UTR中的选择性剪接调节。与该假设一致，我们发现从保守的uAUC开始的开放阅读框显著短于从非保守的uAUC开始的开放阅读框，这可能是由于选择优化衰减水平。
By comparing sequences of human, mouse and rat orthologous genes, we show that in 5′-untranslated regions (5′-UTRs) of mammalian cDNAs but not in 3′-UTRs or coding sequences, AUG is conserved to a significantly greater extent than any of the other 63 nt triplets. This effect is likely to reflect, primarily, bona fide evolutionary conservation, rather than cDNA annotation artifacts, because the excess of conserved upstream AUGs (uAUGs) is seen in 5′-UTRs containing stop codons in-frame with the start AUG and many of the conserved AUGs are found in different frames, consistent with the location in authentic non-coding sequences. Altogether, conserved uAUGs are present in at least 20–30% of mammalian genes. Qualitatively similar results were obtained by comparison of orthologous genes from different species of the yeast genus Saccharomyces. Together with the observation that mammalian and yeast 5′-UTRs are significantly depleted in overall AUG content, these findings suggest that AUG triplets in 5′-UTRs are subject to the pressure of purifying selection in two opposite directions: the uAUGs that have no specific function tend to be deleterious and get eliminated during evolution, whereas those uAUGs that do serve a function are conserved. Most probably, the principal role of the conserved uAUGs is attenuation of translation at the initiation stage, which is often additionally regulated by alternative splicing in the mammalian 5′-UTRs. Consistent with this hypothesis, we found that open reading frames starting from conserved uAUGs are significantly shorter than those starting from non-conserved uAUGs, possibly, owing to selection for optimization of the level of attenuation.
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影响因子：
5.8
作者：
Kochetov, AV;Ponomarenko, MP;Kolchanov, NA
通讯作者：
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3.5
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影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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