Global Organization of a Positive-strand RNA Virus Genome

PLoS Pathogens

Baodong Wu¹  K. Andrew White¹  Sylvie Morin²  Moriam O. Ore²  Jörg Grigull³ 

[1] Department of Biology, York University, Toronto, Ontario, Canada;Department of Chemistry, York University, Toronto, Ontario, Canada;Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada

关键词: RNA structure;    Viral genomics;    Viral structure;    Structural genomics;    RNA viruses;    Invertebrate genomics;    RNA stem-loop structure;    Plant genomics;   

DOI  :  10.1371/journal.ppat.1003363

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The genomes of plus-strand RNA viruses contain many regulatory sequences and structures that direct different viral processes. The traditional view of these RNA elements are as local structures present in non-coding regions. However, this view is changing due to the discovery of regulatory elements in coding regions and functional long-range intra-genomic base pairing interactions. The ∼4.8 kb long RNA genome of the tombusvirus tomato bushy stunt virus (TBSV) contains these types of structural features, including six different functional long-distance interactions. We hypothesized that to achieve these multiple interactions this viral genome must utilize a large-scale organizational strategy and, accordingly, we sought to assess the global conformation of the entire TBSV genome. Atomic force micrographs of the genome indicated a mostly condensed structure composed of interconnected protrusions extending from a central hub. This configuration was consistent with the genomic secondary structure model generated using high-throughput selective 2′-hydroxyl acylation analysed by primer extension (i.e. SHAPE), which predicted different sized RNA domains originating from a central region. Known RNA elements were identified in both domain and inter-domain regions, and novel structural features were predicted and functionally confirmed. Interestingly, only two of the six long-range interactions known to form were present in the structural model. However, for those interactions that did not form, complementary partner sequences were positioned relatively close to each other in the structure, suggesting that the secondary structure level of viral genome structure could provide a basic scaffold for the formation of different long-range interactions. The higher-order structural model for the TBSV RNA genome provides a snapshot of the complex framework that allows multiple functional components to operate in concert within a confined context.

【 授权许可】

CC BY