TRANSLATION OF ENCEPHALOMYOCARDITIS VIRUS-RNA - PARAMETERS INFLUENCING THE SELECTION OF THE INTERNAL INITIATION SITE
TRANSLATION OF ENCEPHALOMYOCARDITIS VIRUS-RNA - PARAMETERS INFLUENCING THE SELECTION OF THE INTERNAL INITIATION SITE
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DOI：
10.1002/j.1460-2075.1994.tb06431.x
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发表时间：
1994-04-01
期刊：
影响因子：
11.4
通讯作者：
JACKSON, RJ
中科院分区：
文献类型：
--
作者：
KAMINSKI, A;BELSHAM, GJ;JACKSON, RJ
脑心肌炎病毒翻译的起始点是内部核糖体仅从AUG密码子的5'端第11位进入，该密码子位于序列中3个AUG密码子的中心。它位于一个在相关病毒中保守的寡聚嘧啶通道下游约25nt处。由于寡聚嘧啶基团与AUG-10/11之间的序列保守性较差，可能仅作为间隔序列，因此在体外和体内研究了该间隔长度对AUG三个密码子起始频率的影响。11个残基的缺失导致几乎完全在AUG-12启动，但总体效率显著降低。8个残基的插入导致AUG-10起始频率增加15倍，而AUG-11起始频率降低。较长的插入在不改变起始位点偏好的情况下降低了总体效率。在野生型间距下，嘌呤完全取代低聚嘧啶链导致起始效率降低30-35%，部分取代仅降低10-15%。因此，内部起始机制选择起始位点部分基于其与上游元件的距离，其中寡聚嘧啶通道不是最关键的，但由于尚不清楚的原因，对AUG-11的偏好重叠在这种选择上。
The initiation of encephalomyocarditis virus translation is by internal ribosome entry exclusively at the 11th AUG codon from the 5'-end, which is the central of the three AUG codons in the sequence..ACGAUGAUAAUAUGGCCACAACCAUG.., and is located some 25 nt downstream from an oligopy rimidine tract conserved amongst related viruses. As the sequences between the oligopyrimidine tract and AUG-10/11 are poorly conserved and thus possibly serve only as a spacer, the influence of this spacer length on initiation frequency at the three AUG codons was examined in vitro and in vivo. Deletion of 11 residues resulted in initiation almost exclusively at AUG-12 but at significantly reduced overall efficiency. Insertion of eight residues caused a 15-fold increase in initiation frequency at AUG-10 and a decrease at AUG-11. Longer insertions reduced overall efficiency without changing the initiation site preferences. With the wild-type spacing, complete substitution of the oligopyrimidine tract by purines caused a 30-35% decrease in initiation efficiency, and partial substitution only a 10-15% decrease. Thus the internal initiation mechanism selects the initiation site partly on the basis of its distance from upstream elements, of which the oligopyrimidine tract is not the most critical, but for reasons not yet understood a preference for AUG-11 is superimposed on this selection.