SL1 revisited: functional analysis of the structure and conformation of HIV-1 genome RNA.
SL1 revisited: functional analysis of the structure and conformation of HIV-1 genome RNA.
复制标题
DOI：
10.1186/s12977-016-0310-9
复制
发表时间：
2016-11-11
期刊：
影响因子：
3.3
通讯作者：
Sakuragi JI
中科院分区：
文献类型：
--
作者：
Sakuragi S;Yokoyama M;Shioda T;Sato H;Sakuragi JI
HIV的二聚体起始位点/二聚体连接序列（DIS/DLS）区域位于病毒基因组的5′端，可形成复杂的二级/三级结构。在这种结构中，茎环1（SL 1）被认为是最重要的，并且是二聚化的关键，因为SL 1的序列和预测的二级结构在各种病毒亚型中高度稳定和保守。特别是，六个碱基的回文序列总是存在于SL 1的发夹环，并且在基因组RNA的两条链之间的该位置处形成吻环结构被认为触发二聚化。虽然SL 1的高阶结构模型被广泛接受，甚至最近被否定，但仍有空间考虑描述体内（病毒体或细胞）的功能性SL 1结构。在这项研究中，我们进行了几项分析，以确定核苷酸和/或碱基配对内的HIV-1基因组二聚化，双糖苷化，重组和感染性是必要的。我们意外地发现，一些被认为有助于茎形成的核苷酸不影响二聚化或感染性。另一方面，我们发现参与茎形成的一个G-C碱基对可能作为另一个二聚体相互作用位点。我们还报告了我们对回文序列在病毒复制中的作用的进一步研究。总的来说，我们的目标是在HIV-1病毒生命周期中组装一个更全面的SL 1功能图。我们在HIV-1 DLS中发现了SL 1新结构的几种可能性。新提出的结构模型表明，SL 1的发夹环似乎更大，基因组二聚化过程可能包括比以前理解的更复杂的机制。仍需要进一步的研究，以充分了解艾滋病毒的基因组包装和二聚化。本文的在线版本（doi：10.1186/s12977-016-0310-9）包含补充材料，可供授权用户使用。
The dimer initiation site/dimer linkage sequence (DIS/DLS) region of HIV is located on the 5′ end of the viral genome and suggested to form complex secondary/tertiary structures. Within this structure, stem-loop 1 (SL1) is believed to be most important and an essential key to dimerization, since the sequence and predicted secondary structure of SL1 are highly stable and conserved among various virus subtypes. In particular, a six-base palindromic sequence is always present at the hairpin loop of SL1 and the formation of kissing-loop structure at this position between the two strands of genomic RNA is suggested to trigger dimerization. Although the higher-order structure model of SL1 is well accepted and perhaps even undoubted lately, there could be stillroom for consideration to depict the functional SL1 structure while in vivo (in virion or cell). In this study, we performed several analyses to identify the nucleotides and/or basepairing within SL1 which are necessary for HIV-1 genome dimerization, encapsidation, recombination and infectivity. We unexpectedly found that some nucleotides that are believed to contribute the formation of the stem do not impact dimerization or infectivity. On the other hand, we found that one G–C basepair involved in stem formation may serve as an alternative dimer interactive site. We also report on our further investigation of the roles of the palindromic sequences on viral replication. Collectively, we aim to assemble a more-comprehensive functional map of SL1 on the HIV-1 viral life cycle. We discovered several possibilities for a novel structure of SL1 in HIV-1 DLS. The newly proposed structure model suggested that the hairpin loop of SL1 appeared larger, and genome dimerization process might consist of more complicated mechanism than previously understood. Further investigations would be still required to fully understand the genome packaging and dimerization of HIV. The online version of this article (doi:10.1186/s12977-016-0310-9) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
14.9
作者：
Kieken F;Paquet F;Brulé F;Paoletti J;Lancelot G
通讯作者：
Lancelot G
影响因子：
5.4
作者：
Clever, JL;Parslow, TG
通讯作者：
Parslow, TG
DOI：
10.1101/sqb.1974.039.01.096
发表时间：
1974-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
KUNG, HJ;BAILEY, JM;MCALLISTER, RM
通讯作者：
MCALLISTER, RM
影响因子：
3.8
作者：
GRAHAM, FL;SMILEY, J;NAIRN, R
通讯作者：
NAIRN, R
影响因子：
5.4
作者：
ADACHI, A;GENDELMAN, HE;MARTIN, MA
通讯作者：
MARTIN, MA