HIV-RNA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 在复制过程中，HIV-1病毒从含有大量过量的细胞和剪接的病毒RNA的细胞库中选择性地包装其全长未剪接RNA基因组的两个拷贝。了解基因组包装机制对于制定新的抗艾滋病战略至关重要。对病毒RNA基因组片段的高分辨率结构研究可以为揭示其机制提供有价值的信息。 最近的体内研究表明，全长HIV-1 5 ′-非翻译区（UTR）和gag基因的上游编码区负责有效的基因组包装。然而，由于共振重叠和峰增宽，大分子尺寸（~3000 kDa）给NMR表征带来了极大的困难。为了降低光谱的复杂性，我们采用片段同位素标记的RNA样品来研究完整的352个核苷酸的HIV-1 5 <$-UTR结构。如果cryo-EM可以为这种大RNA提供一些结构限制，这将是至关重要的。此外，我们期望cryo-EM可以“可视化”二聚化后的5 '-UTR构象变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During the replication process, HIV-1 viruses selectively package two copies of their full-length unspliced RNA genomes from a cellular pool that contains a substantial excess of cellular and spliced viral RNAs. Understanding the genome packaging mechanism will be essential for the development of new anti-AIDS strategies. High-resolution structural studies of the viral RNA genome fragment can provide valuable information in unraveling the mechanism. Recent in vivo studies have indicated that the full length HIV-1 5¿-untranslated region (UTR) and upstream coding regions of the gag gene are responsible for efficient genome packaging. However, the large molecular size (~3000 kDa) has posed extreme difficulties for NMR characterizations due to the resonance overlap and peak broadening. To reduce the complexity of spectra, we employed segmental isotope labeled RNA samples to investigate the intact 352 nucleotide HIV-1 5¿-UTR structure. It will be essential if cryo-EM can provide some structural constraints for this large RNA. In addition, we are expecting that cryo-EM can "visualize" the 5'-UTR conformation change upon dimerization.