The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620604
Title:
The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon.
Authors:
Moes, Lorin; Wirth, Manfred ( 0000-0002-3094-4227 )
Abstract:
Bovine viral diarrhea virus (BVDV) is the prototype representative of the pestivirus genus in the Flaviviridae family. It has been shown that the initiation of translation of BVDV RNA occurs by an internal ribosome entry mechanism mediated by the 5' untranslated region of the viral RNA 1. The 5' and 3' boundaries of the IRES of the cytopathic BVDV NADL have been mapped and it has been suggested that the IRES extends into the coding of the BVDV polyprotein 2. A putative pseudoknot structure has been recognized in the BVDV 5'UTR in close proximity to the AUG start codon. A pseudoknot structure is characteristic for flavivirus IRESes and in the case of the closely related classical swine fever virus (CSFV) and the more distantly related Hepatitis C virus (HCV) pseudoknot function in translation has been demonstrated.; To characterize the BVDV IRESes in detail, we studied the BVDV translational initiation by transfection of dicistronic expression plasmids into mammalian cells. A region coding for the amino terminus of the BVDV SD-1 polyprotein contributes considerably to efficient initiation of translation. The translation efficiency mediated by the IRES of BVDV strains NADL and SD-1 approximates the poliovirus type I IRES directed translation in BHK cells. Compared to the poliovirus IRES increased expression levels are mediated by the BVDV IRES of strain SD-1 in murine cell lines, while lower levels are observed in human cell lines. Site directed mutagenesis revealed that a RNA pseudoknot upstream of the initiator AUG is an important structural element for IRES function. Mutants with impaired ability to base pair in stem I or II lost their translational activity. In mutants with repaired base pairing either in stem 1 or in stem 2 full translational activity was restored. Thus, the BVDV IRES translation is dependent on the pseudoknot integrity. These features of the pestivirus IRES are reminiscent of those of the classical swine fever virus, a pestivirus, and the hepatitis C viruses, another genus of the Flaviviridae.; The IRES of the non-cytopathic BVDV SD-1 strain displays features known from other pestivirus IRESes. The predicted pseudoknot in the 5'UTR of BVDV SD-1 virus represents an important structural element in BVDV translation.
Citation:
The internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon. 2007, 4:124 Virol. J.
Journal:
Virology journal
Issue Date:
22-Nov-2007
URI:
http://hdl.handle.net/10033/620604
DOI:
10.1186/1743-422X-4-124
PubMed ID:
18034871
ISSN:
1743-422X
Appears in Collections:
research group of structural biology of autophagy (SBAU)

Full metadata record

DC FieldValue Language
dc.contributor.authorMoes, Lorin-
dc.contributor.authorWirth, Manfred-
dc.date.accessioned2016-11-29T08:51:06Z-
dc.date.available2016-11-29T08:51:06Z-
dc.date.issued2007-11-22-
dc.identifier.citationThe internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon. 2007, 4:124 Virol. J.-
dc.identifier.issn1743-422X-
dc.identifier.pmid18034871-
dc.identifier.doi10.1186/1743-422X-4-124-
dc.identifier.urihttp://hdl.handle.net/10033/620604-
dc.description.abstractBovine viral diarrhea virus (BVDV) is the prototype representative of the pestivirus genus in the Flaviviridae family. It has been shown that the initiation of translation of BVDV RNA occurs by an internal ribosome entry mechanism mediated by the 5' untranslated region of the viral RNA 1. The 5' and 3' boundaries of the IRES of the cytopathic BVDV NADL have been mapped and it has been suggested that the IRES extends into the coding of the BVDV polyprotein 2. A putative pseudoknot structure has been recognized in the BVDV 5'UTR in close proximity to the AUG start codon. A pseudoknot structure is characteristic for flavivirus IRESes and in the case of the closely related classical swine fever virus (CSFV) and the more distantly related Hepatitis C virus (HCV) pseudoknot function in translation has been demonstrated.-
dc.description.abstractTo characterize the BVDV IRESes in detail, we studied the BVDV translational initiation by transfection of dicistronic expression plasmids into mammalian cells. A region coding for the amino terminus of the BVDV SD-1 polyprotein contributes considerably to efficient initiation of translation. The translation efficiency mediated by the IRES of BVDV strains NADL and SD-1 approximates the poliovirus type I IRES directed translation in BHK cells. Compared to the poliovirus IRES increased expression levels are mediated by the BVDV IRES of strain SD-1 in murine cell lines, while lower levels are observed in human cell lines. Site directed mutagenesis revealed that a RNA pseudoknot upstream of the initiator AUG is an important structural element for IRES function. Mutants with impaired ability to base pair in stem I or II lost their translational activity. In mutants with repaired base pairing either in stem 1 or in stem 2 full translational activity was restored. Thus, the BVDV IRES translation is dependent on the pseudoknot integrity. These features of the pestivirus IRES are reminiscent of those of the classical swine fever virus, a pestivirus, and the hepatitis C viruses, another genus of the Flaviviridae.-
dc.description.abstractThe IRES of the non-cytopathic BVDV SD-1 strain displays features known from other pestivirus IRESes. The predicted pseudoknot in the 5'UTR of BVDV SD-1 virus represents an important structural element in BVDV translation.-
dc.languageENG-
dc.rightsArchived with thanks to Virology journalen
dc.subject.mesh5' Untranslated Regions-
dc.subject.meshAnimals-
dc.subject.meshCattle-
dc.subject.meshCell Line-
dc.subject.meshCodon, Initiator-
dc.subject.meshDiarrhea Viruses, Bovine Viral-
dc.subject.meshHeLa Cells-
dc.subject.meshHumans-
dc.subject.meshNucleic Acid Conformation-
dc.subject.meshProtein Biosynthesis-
dc.subject.meshRNA, Viral-
dc.subject.meshRegulatory Sequences, Nucleic Acid-
dc.subject.meshStructure-Activity Relationship-
dc.subject.meshTranscription, Genetic-
dc.titleThe internal initiation of translation in bovine viral diarrhea virus RNA depends on the presence of an RNA pseudoknot upstream of the initiation codon.-
dc.identifier.journalVirology journal-
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