HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome

被引：60

作者：

Mouzakis, Kathryn D. ^{[1
]}

Lang, Andrew L. ^{[1
]}

Vander Meulen, Kirk A. ^{[1
]}

Easterday, Preston D. ^{[1
]}

Butcher, Samuel E. ^{[1
]}

机构：

[1] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA

来源：

NUCLEIC ACIDS RESEARCH | 2013年 / 41卷 / 03期

基金：

美国国家卫生研究院;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; NEAREST-NEIGHBOR MODEL; SECONDARY STRUCTURE; THERMODYNAMIC PARAMETERS; MUTATIONAL ANALYSIS; STIMULATORY SIGNAL; PSEUDOKNOT; SITE; TRANSLATION; PROTEASE;

D O I：

10.1093/nar/gks1254

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 34 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 genonnic 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.

引用

页码：1901 / 1913

页数：13