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Dynamic RNA structures in the dengue virus genome Featured

Dengue virus is an important human pathogen that belongs to the Flaviviridae family. The viral genome is a single molecule of RNA of positive polarity that plays multiple roles during the viral life cycle. Besides encoding the viral proteins, the genome contains RNA structures that regulate different viral processes.


Iglesias NG and Gamarnik AG

(Fundación instituto Leloir-CONiCeT; Buenos Aires, Argentina)

An important feature of dengue and other flavivirus genomes is the presence of inverted complementary sequences at the ends of the molecule that mediate long-range RNA-RNA interaction and genome cyclization. Recent studies have demonstrated that alternative conformations of the genome are necessary for infectivity. In this review, we discuss the current understanding of the function of different RNA elements that modulate dengue virus replication and provide new ideas of how dynamic RNA structures participate in the viral processes.

The genome of plus strand RNA viruses contains a wide variety of RNA signals with information to regulate fundamental processes of viral life cycles. Upon infection, the incoming genome serves as mRNA for translation, template for RNA synthesis and substrate for encapsidation. These processes must be temporally regulated to ensure efficient utilization of the genome and viral spread. RNA structures function as promoters, enhancers and repressors of translation, transcription, replication and encapsidation.1-15 In addition, viral RNAs participate in triggering or avoiding the antiviral host response.16,17 Viral RNA genomes are dynamic molecules. Their secondary and tertiary structures change throughout the viral life cycle responding to alteration of the environment in the infected cell. RNA plasticity is governed by nucleotide sequences, local and long-range RNA-RNA interactions and association with viral and host proteins or ligands. Locations of enhancers, promoters or modulators of viral processes have been found in coding and uncoding regions of viral genomes.1,18-29 Although translation initiation takes place at the 5' end and RNA replication initiates at the 3' end of the genome, cis-acting elements required for translation initiation can be found at the 3' end of the viral RNA while elements necessary for initiation of RNA synthesis can be located at the 5' end of the viral RNA.13,27,30-34 These observations highlight the crucial role of complex tertiary interactions that span thousands of nucleotides in viral genomes (reviewed in ref. 35–37).

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