Abstract
RNA virus genomes are multifunctional entities endowed with conserved structural elements that control translation, replication and encapsidation, among other processes. The preservation of these structural RNA elements constraints the genomic sequence variability. The hepatitis C virus (HCV) genome is a positive, single-stranded RNA molecule with numerous conserved structural elements that manage different steps during the infection cycle. Their function is ensured by the association of protein factors, but also by the establishment of complex, active, long-range RNA-RNA interaction networks-the so-called HCV RNA interactome. This review describes the RNA genome functions mediated via RNA-RNA contacts, and revisits some canonical ideas regarding the role of functional high-order structures during the HCV infective cycle. By outlining the roles of long-range RNA-RNA interactions from translation to virion budding, and the functional domains involved, this work provides an overview of the HCV genome as a dynamic device that manages the course of viral infection.
Highlights
The function of RNA molecules is dependent on their sequence, and on their structure
RNA structure is maintained by the widespread establishment of hydrogen bonds between different nucleotides, yielding a set of loops and stems that define the overall folding of the molecule
We showed that the bulge of the 5BSL3.2 at the 3 end of the open reading frame (ORF) directly interacts with the apical loop of subdomain IIId within the internal ribosome entry site (IRES) (Figure 4B)
Summary
The function of RNA molecules is dependent on their sequence, and on their structure. Viral RNA genomes are compact entities with the capacity to perform different functions during the infective cycle, as well as carrying protein-coding information Such genomic plasticity confers significant adaptive capacity, allowing new hosts and molecular contexts to be explored, promoting the emergence of new diseases. Workable replication culture and infectious systems provide a complete picture [8,9] Along with these advances, the development of the “omics” field in molecular biology has led to powerful high-throughput methodologies that return huge amounts of data from just a single experiment. The development of the “omics” field in molecular biology has led to powerful high-throughput methodologies that return huge amounts of data from just a single experiment These advances have filled the gaps in our knowledge of some virus cycle control systems, and have revealed the importance of long-range RNA-RNA interactions in the intracellular phase of infection. An overview of the participation of the HCV RNA genome in all stages of the virus life cycle is provided, and the ubiquity of long-range RNA-RNA interactions in other viral models discussed
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