根据对从感染性病毒颗粒提取出的真实HIV RNA所做分析,研究人员已确定了一个完整HIV-1 RNA基因组的二级结构。
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。SHAPE技术(由引物延伸催化的高通量选择性2’-羟基酰化)被用来对由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(其中一些发布在本期封面上),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。从这项工作获得的信息,有可能使我们对HIV-1生物学有更好的认识,并有可能导致新的抗逆转录病毒干预方法的问世。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 460, 711-716 (6 August 2009) | doi:10.1038/nature08237; Received 11 May 2009; Accepted 22 June 2009
Architecture and secondary structure of an entire HIV-1 RNA genome
Joseph M. Watts1, Kristen K. Dang2, Robert J. Gorelick5, Christopher W. Leonard1, Julian W. Bess Jr5, Ronald Swanstrom3, Christina L. Burch4 & Kevin M. Weeks1
1 Department of Chemistry,
2 Department of Biomedical Engineering,
3 Linenberger Cancer Center,
4 Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA
5 AIDS and Cancer Virus Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702-1201, USA
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.