Nature封面：艾滋病病毒完整基因组

　　

来自美国北卡罗来那大学化学系，生物医药工程的研究人员确定了一个完整HIV-1 RNA基因组的二级结构，这是首次破译艾滋病病毒完整基因组。这一研究成果公布在Nature杂志上的首页上。

这项研究的对象是感染性病毒颗粒提取出的真实HIV RNA，单链病毒RNA基因组内的二级结构已知具有几种功能和调控作用，但此前研究人员尚未对任何病毒的完整RNA进行过全面分析。

在这篇文章中，研究人员利用SHAPE技术（由引物延伸催化的高通量选择性2’-羟基酰化），对由HIV-1 RNA基因组形成的所有结构进行定性。由此，他们发现了无数高结构性主题，其中很多主题的功能也可以被推断出来。重要的是，RNA结构元素的存在被发现影响蛋白的翻译，有助于正确的蛋白折叠。这些结果表明，HIV-1基因组有结构，其构成元素对病毒适应性非常关键。

艾滋病病毒的RNA结构对病毒感染周期中的多个阶段都有影响。所谓感染周期，是指病毒从识别到进入细胞并进行攻击的一系列步骤。研究人员认为，掌握完整的艾滋病病毒基因组后，他们就可以设计实验，查明某个特定基因在病毒感染人体过程中发挥什么作用，在这一基础上有望开发出对付艾滋病病毒的新药。
 

原文摘要：

Architecture and secondary structure of an entire HIV-1 RNA genome

Single-stranded RNA viruses encompass broad classes of infectious agents and cause the common cold, cancer, AIDS and other serious health threats. Viral replication is regulated at many levels, including the use of conserved genomic RNA structures. Most potential regulatory elements in viral RNA genomes are uncharacterized. Here we report the structure of an entire HIV-1 genome at single nucleotide resolution using SHAPE, a high-throughput RNA analysis technology. The genome encodes protein structure at two levels. In addition to the correspondence between RNA and protein primary sequences, a correlation exists between high levels of RNA structure and sequences that encode inter-domain loops in HIV proteins. This correlation suggests that RNA structure modulates ribosome elongation to promote native protein folding. Some simple genome elements previously shown to be important, including the ribosomal gag-pol frameshift stem-loop, are components of larger RNA motifs. We also identify organizational principles for unstructured RNA regions, including splice site acceptors and hypervariable regions. These results emphasize that the HIV-1 genome and, potentially, many coding RNAs are punctuated by previously unrecognized regulatory motifs and that extensive RNA structure constitutes an important component of the genetic code.