Novel cis-acting element within the capsid-coding region enhances flavivirus viral-RNA replication by regulating genome cyclization.
J Virol
; 87(12): 6804-18, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23576500
cis-Acting elements in the viral genome RNA (vRNA) are essential for the translation, replication, and/or encapsidation of RNA viruses. In this study, a novel conserved cis-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. The downstream of 5' cyclization sequence (5'CS) pseudoknot (DCS-PK) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. Using dengue virus as a model, we show that DCS-PK enhances vRNA replication and that its function depends on its secondary structure and specific primary sequence. Mutagenesis revealed that the highly conserved stem 1 and loop 2, which are involved in potential loop-helix interactions, are crucial for DCS-PK function. A predicted loop 1-stem 3 base triple interaction is important for the structural stability and function of DCS-PK. Moreover, the function of DCS-PK depends on its position relative to the 5'CS, and the presence of DCS-PK facilitates the formation of 5'-3' RNA complexes. Taken together, our results reveal that the cis-acting element DCS-PK enhances vRNA replication by regulating genome cyclization, and DCS-PK might interplay with other cis-acting elements to form a functional vRNA cyclization domain, thus playing critical roles during the flavivirus life cycle and evolution.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
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RNA Viral
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Regulação Viral da Expressão Gênica
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Capsídeo
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Elementos Facilitadores Genéticos
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Genoma Viral
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Flavivirus
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Virol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China