期刊
NUCLEIC ACIDS RESEARCH
卷 42, 期 1, 页码 567-582出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkt841
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资金
- Spanish Ministerio de Ciencia e Innovacion [BFU2009-08137, BIO2010-20696]
- Spanish Ministerio de Economia y Competitividad [BFU2012-31213]
- Junta de Andalucia [CVI-7430]
- Spanish Council for Scientific Research [201120E004]
- FEDER funds from the EU
- CIBERehd
- Instituto de Salud Carlos III
The hepatitis C virus (HCV) RNA genome contains multiple structurally conserved domains that make long-distance RNA-RNA contacts important in the establishment of viral infection. Microarray antisense oligonucelotide assays, improved dimethyl sulfate probing methods and 20 acylation chemistry (selective 2'-hydroxyl acylation and primer extension, SHAPE) showed the folding of the genomic RNA 30 end to be regulated by the internal ribosome entry site (IRES) element via direct RNA-RNA interactions. The essential cis-acting replicating element (CRE) and the 3'X-tail region adopted different 3D conformations in the presence and absence of the genomic RNA 50 terminus. Further, the structural transition in the 3'X-tail from the replication-competent conformer (consisting of three stem-loops) to the dimerizable form (with two stem-loops), was found to depend on the presence of both the IRES and the CRE elements. Complex interplay between the IRES, the CRE and the 3'X-tail region would therefore appear to occur. The preservation of this RNA-RNA interacting network, and the maintenance of the proper balance between different contacts, may play a crucial role in the switch between different steps of the HCV cycle.
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