End-to-end crosstalk within the hepatitis C virus genome mediates the conformational switch of the 3'X-tail region.
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 oligonucleotide assays, improved dimethyl sulfate probing methods and 2' acylation chemistry (selective 2'-hydroxyl acylation and primer extension, SHAPE) showed the folding of the genomic RNA 3' 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 5' 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.
Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS Granada, Avda. del Conocimiento s/n, Armilla, 18016 Granada, Spain, Unidad de Genómica, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, PTS Granada, Avda. del Conocimiento s/n, Armilla, 18016 Granada, Spain, Laboratorio de Evolución Molecular, Centro de Astrobiología (CSIC-INTA), Carretera de Ajalvir km 4, 28850 Torrejón de Ardoz, Madrid, Spain and Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Spain.
Cristina
C
Romero-López
Alicia
A
Barroso-Deljesus
Ana
A
García-Sacristán
Carlos
C
Briones
Alfredo
A
Berzal-Herranz
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D001483:Base Sequence; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D059370:RNA Folding; D012367:RNA, Viral / Q000737:chemistry*
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D012367:RNA, Viral