HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome.
HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome.
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DOI：
10.1093/nar/gks1254
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发表时间：
2013-02-01
影响因子：
14.9
通讯作者：
Butcher SE
中科院分区：
文献类型：
--
作者：
Mouzakis KD;Lang AL;Vander Meulen KA;Easterday PD;Butcher SE
人类免疫缺陷病毒（HIV）需要程序化的-1核糖体移码来表达Pol基因。HIV移码位点由一个七核苷酸滑动序列（UUUUUUA），随后是一个间隔区和下游RNA茎环结构组成。在这里，我们研究RNA结构在促进-1移码中的作用。系统地改变茎环，以消除局部和整体热力学稳定性对移码效率的贡献。未观察到总体稳定性和移码效率之间的相关性。相比之下，移码效率和茎环中前3-4 bp的局部热力学稳定性之间存在强相关性，预测当核糖体在滑动位点暂停时，其驻留在mRNA入口通道的开口处。间隔区中的插入或缺失似乎相应地改变了在滑动位点下游8 nt处遇到的碱基对的身份。最后，研究了周围基因组二级结构的作用，发现其对移码效率具有适度的影响，这与基因组二级结构通过影响总翻译速率来减弱移码的假设一致。
The human immunodeficiency virus (HIV) requires a programmed −1 ribosomal frameshift for Pol gene expression. The HIV frameshift site consists of a heptanucleotide slippery sequence (UUUUUUA) followed by a spacer region and a downstream RNA stem–loop structure. Here we investigate the role of the RNA structure in promoting the −1 frameshift. The stem–loop was systematically altered to decouple the contributions of local and overall thermodynamic stability towards frameshift efficiency. No correlation between overall stability and frameshift efficiency is observed. In contrast, there is a strong correlation between frameshift efficiency and the local thermodynamic stability of the first 3–4 bp in the stem–loop, which are predicted to reside at the opening of the mRNA entrance channel when the ribosome is paused at the slippery site. Insertion or deletions in the spacer region appear to correspondingly change the identity of the base pairs encountered 8 nt downstream of the slippery site. Finally, the role of the surrounding genomic secondary structure was investigated and found to have a modest impact on frameshift efficiency, consistent with the hypothesis that the genomic secondary structure attenuates frameshifting by affecting the overall rate of translation.
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测试最接近的邻居模型的规范RNA碱基对：GU参数的修订。
影响因子：
2.9
作者：
Chen JL;Dishler AL;Kennedy SD;Yildirim I;Liu B;Turner DH;Serra MJ
通讯作者：
Serra MJ
DOI：
10.1073/pnas.0905046106
发表时间：
2009-08-04
影响因子：
11.1
作者：
Chen, Gang;Chang, Kung-Yao;Tinoco, Ignacio, Jr.
通讯作者：
Tinoco, Ignacio, Jr.
影响因子：
3.3
作者：
Das AT;Vrolijk MM;Harwig A;Berkhout B
通讯作者：
Berkhout B
影响因子：
5
作者：
Giedroc, David P.;Cornish, Peter V.
通讯作者：
Cornish, Peter V.
影响因子：
5.6
作者：
Green L;Kim CH;Bustamante C;Tinoco I Jr
通讯作者：
Tinoco I Jr