ADHERENCE TO THE FIRST-AUG RULE WHEN A SECOND AUG CODON FOLLOWS CLOSELY UPON THE FIRST
ADHERENCE TO THE FIRST-AUG RULE WHEN A SECOND AUG CODON FOLLOWS CLOSELY UPON THE FIRST
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DOI：
10.1073/pnas.92.7.2662
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发表时间：
1995-03-28
影响因子：
11.1
通讯作者：
KOZAK, M
中科院分区：
文献类型：
--
作者：
KOZAK, M
真核生物核糖体只在5'端AUG密码子启动翻译的规则在罕见的情况下被废除。已经提出允许双重起始的一种情况是第二个AUG密码子的紧密并置。一个可能的机制可能是，扫描40 S核糖体亚基来回摆动，而不是干净地停止在第一个AUG。这一假设似乎被排除在本文提出的证据，在某些mRNA中，两个接近AUG密码子的第一个是唯一识别。为了实现这一点，5'近端AUG必须具有完整的共有序列;即使是小的偏离也允许通过漏扫描到达第二个附近的AUG密码子。当第二个AUG密码子从第一个移动一定距离时，这种依赖于密码子的泄漏扫描意外地失败。基于在起始与延伸条件下分析远下游AUG密码子的可及性，一个可能的解释是从5'近端起始位点推进的80 S延伸核糖体可以掩盖潜在的下游起始位点。
The rule that eukaryotic ribosomes initiate translation exclusively at the 5' proximal AUG codon is abrogated under rare conditions. One circumstance that has been suggested to allow dual initiation is close apposition of a second AUG codon. A possible mechanism might be that the scanning 40S ribosomal subunit flutters back and forth instead of stopping cleanly at the first AUG. This hypothesis seems to be ruled out by evidence presented herein that in certain mRNAs, the first of two close AUG codons is recognized uniquely. To achieve this, the 5' proximal AUG has to be provided with the full consensus sequence; even small departures allow a second nearby AUG codon to be reached by leaky scanning. This contest-dependent leaky scanning unexpectedly fails when the second AUG codon is moved some distance from the first. A likely explanation, based on analyzing the accessibility of a far-downstream AUG codon under conditions of initiation versus elongation, is that 80S elongating ribosomes advancing from the 5' proximal start site can mask potential downstream start sites.