Translation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97770
Title:
Translation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame.
Authors:
Stacey, Simon N; Jordan, Deborah; Snijders, P J; Mackett, Mike; Walboomers, J M; Arrand, John R
Abstract:
In this study we investigated the translational capacities of bicistronic and spliced mRNAs originating from the E6 and E7 regions of the high-risk genital human papillomavirus type 16 (HPV-16) and the low-risk HPV-11. For HPV-16 it was found, unexpectedly, that E7 protein could be translated from full-length bicistronic E6-E7 mRNAs. E6*I and E6*II splicing events were not required for E7 synthesis, nor did splicing increase the efficiency of E7 translation significantly. In cells, E7 synthesis from all known naturally occurring mRNA structures was very inefficient compared with that from synthetic monocistronic controls, suggesting that HPV-16 employs translational mechanisms to restrict E7 protein levels. For HPV-11, only RNAs initiated at the P264 promoter, located within the E6 open reading frame, were capable of providing an efficient template for E7 synthesis. P264-initiated mRNAs were as efficient in vivo as monocistronic controls, suggesting that the low-risk HPV-11 does not limit E7 synthesis by translational mechanisms. A detailed analysis of HPV-16 templates by using site-directed mutagenesis showed that the majority of ribosomes which ultimately translate E7 have not reinitiated after translating some or all of the upstream open reading frames. The data support a model in which the failure of 40S ribosomal initiation complexes to recognize the E6 AUG renders them capable of proceeding efficiently to translate E7.
Affiliation:
Department of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom.
Citation:
Translation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame. 1995, 69 (11):7023-31 J. Virol.
Journal:
Journal of Virology
Issue Date:
Nov-1995
URI:
http://hdl.handle.net/10541/97770
PubMed ID:
7474122
Type:
Article
Language:
en
ISSN:
0022-538X
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorStacey, Simon Nen
dc.contributor.authorJordan, Deborahen
dc.contributor.authorSnijders, P Jen
dc.contributor.authorMackett, Mikeen
dc.contributor.authorWalboomers, J Men
dc.contributor.authorArrand, John Ren
dc.date.accessioned2010-04-30T15:48:45Z-
dc.date.available2010-04-30T15:48:45Z-
dc.date.issued1995-11-
dc.identifier.citationTranslation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame. 1995, 69 (11):7023-31 J. Virol.en
dc.identifier.issn0022-538X-
dc.identifier.pmid7474122-
dc.identifier.urihttp://hdl.handle.net/10541/97770-
dc.description.abstractIn this study we investigated the translational capacities of bicistronic and spliced mRNAs originating from the E6 and E7 regions of the high-risk genital human papillomavirus type 16 (HPV-16) and the low-risk HPV-11. For HPV-16 it was found, unexpectedly, that E7 protein could be translated from full-length bicistronic E6-E7 mRNAs. E6*I and E6*II splicing events were not required for E7 synthesis, nor did splicing increase the efficiency of E7 translation significantly. In cells, E7 synthesis from all known naturally occurring mRNA structures was very inefficient compared with that from synthetic monocistronic controls, suggesting that HPV-16 employs translational mechanisms to restrict E7 protein levels. For HPV-11, only RNAs initiated at the P264 promoter, located within the E6 open reading frame, were capable of providing an efficient template for E7 synthesis. P264-initiated mRNAs were as efficient in vivo as monocistronic controls, suggesting that the low-risk HPV-11 does not limit E7 synthesis by translational mechanisms. A detailed analysis of HPV-16 templates by using site-directed mutagenesis showed that the majority of ribosomes which ultimately translate E7 have not reinitiated after translating some or all of the upstream open reading frames. The data support a model in which the failure of 40S ribosomal initiation complexes to recognize the E6 AUG renders them capable of proceeding efficiently to translate E7.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshCell Line-
dc.subject.meshCercopithecus aethiops-
dc.subject.meshCloning, Molecular-
dc.subject.meshGenes, Viral-
dc.subject.meshGenome, Viral-
dc.subject.meshHela Cells-
dc.subject.meshHumans-
dc.subject.meshMutagenesis, Site-Directed-
dc.subject.meshOncogene Proteins, Viral-
dc.subject.meshOpen Reading Frames-
dc.subject.meshPapillomaviridae-
dc.subject.meshProtein Biosynthesis-
dc.subject.meshRNA Splicing-
dc.subject.meshRNA, Messenger-
dc.subject.meshRecombinant Proteins-
dc.subject.meshRibosomes-
dc.subject.meshTemplates, Genetic-
dc.subject.meshTransfection-
dc.subject.meshViral Structural Proteins-
dc.titleTranslation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame.en
dc.typeArticleen
dc.contributor.departmentDepartment of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom.en
dc.identifier.journalJournal of Virologyen
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