Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis.
Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis.
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DOI：
10.1093/nar/gkx690
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发表时间：
2017-09-29
影响因子：
14.9
通讯作者：
Atkins JF
中科院分区：
文献类型：
--
作者：
Penno C;Kumari R;Baranov PV;van Sinderen D;Atkins JF
HIV GagPol的合成涉及一定比例的核糖体翻译gag基因远端的U6 A移位位点，执行程序性-1核糖体移码事件以进入重叠pol基因。体外研究表明，HIV逆转录酶在相同的移位基序上产生-1和+1 indel，其比率对模板DNA的滑动倾向序列及其5′端相邻碱基所指定的dNTPs的相对浓度比敏感。GGG序列3′端与U6 A移位/滑动位点相邻，这对核糖体移码很重要，在这里显示限制了逆转录酶碱基替换和产物中A运行中的indel“错误”。这里表征的插入缺失具有比模板U的相应数目多或少1个A。具有5个A的cDNA可以产生新的Gag产物，而具有额外碱基7个A的cDNA可能仅是GagPol多蛋白的次要贡献者。一定比例的非核糖体移码衍生的GagPol的合成将与鉴定扰乱GagPol与Gag的比率的治疗上有用的化合物的努力相关，并且与在基因表达中利用特异性聚合酶滑移的程度相关。
Synthesis of HIV GagPol involves a proportion of ribosomes translating a U6A shift site at the distal end of the gag gene performing a programmed -1 ribosomal frameshift event to enter the overlapping pol gene. In vitro studies here show that at the same shift motif HIV reverse transcriptase generates -1 and +1 indels with their ratio being sensitive to the relative concentration ratio of dNTPs specified by the RNA template slippage-prone sequence and its 5′ adjacent base. The GGG sequence 3′ adjacent to the U6A shift/slippage site, which is important for ribosomal frameshifting, is shown here to limit reverse transcriptase base substitution and indel ‘errors’ in the run of A’s in the product. The indels characterized here have either 1 more or less A, than the corresponding number of template U’s. cDNA with 5 A’s may yield novel Gag product(s), while cDNA with an extra base, 7 A’s, may only be a minor contributor to GagPol polyprotein. Synthesis of a proportion of non-ribosomal frameshift derived GagPol would be relevant in efforts to identify therapeutically useful compounds that perturb the ratio of GagPol to Gag, and pertinent to the extent in which specific polymerase slippage is utilized in gene expression.
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DOI：
10.1093/bioinformatics/btr490
发表时间：
2011-11-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Howe EA;Sinha R;Schlauch D;Quackenbush J
通讯作者：
Quackenbush J
影响因子：
4
作者：
Hilimire TA;Bennett RP;Stewart RA;Garcia-Miranda P;Blume A;Becker J;Sherer N;Helms ED;Butcher SE;Smith HC;Miller BL
通讯作者：
Miller BL
DOI：
10.1073/pnas.1421545111
发表时间：
2014-12-16
影响因子：
11.1
作者：
Blaby-Haas, Crysten E.;Padilla-Benavides, Teresita;Merchant, Sabeeha S.
通讯作者：
Merchant, Sabeeha S.
DOI：
10.1073/pnas.89.15.6919
发表时间：
1992-08-01
影响因子：
11.1
作者：
BOYER, JC;BEBENEK, K;KUNKEL, TA
通讯作者：
KUNKEL, TA
影响因子：
17.3
作者：
Dinman, JD;Ruiz-Echevarria, MJ;Peltz, SW
通讯作者：
Peltz, SW