Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Leaky scanning is the predominant mechanism for translation of human papillomavirus type 16 E7 oncoprotein from E6/E7 bicistronic mRNA.
Stacey SN
,
Jordan D
,
Williamson AJ
,
Brown M
,
Coote JH
,
Arrand JR
.
???displayArticle.abstract???
Human papillomaviruses (HPV) are unique in that they generate mRNAs that apparently can express multiple proteins from tandemly arranged open reading frames. The mechanisms by which this is achieved are uncertain and are at odds with the basic predictions of the scanning model for translation initiation. We investigated the unorthodox mechanism by which the E6 and E7 oncoproteins from human papillomavirus type 16 (HPV-16) can be translated from a single, bicistronic mRNA. The short E6 5' untranslated region (UTR) was shown to promote translation as efficiently as a UTR from Xenopus beta-globin. Insertion of a secondary structural element into the UTR inhibited both E6 and E7 expression, suggesting that E7 expression depends on ribosomal scanning from the 5' end of the mRNA. E7 translation was found to be cap dependent, but E6 was more dependent on capping and eIF4F activity than E7. Insertion of secondary structural elements at various points in the region upstream of E7 profoundly inhibited translation, indicating that scanning was probably continuous. Insertion of the E6 region between Renilla and firefly luciferase genes revealed little or no internal ribosomal entry site activity. However when E6 was located at the 5' end of the mRNA, it permitted over 100-fold-higher levels of downstream cistron translation than did the Renilla open reading frame. Internal AUGs in the E6 region with strong or intermediate Kozak sequence contexts were unable to inhibit E7 translation, but initiation at the E7 AUG was efficient and accurate. These data support a model in which E7 translation is facilitated by an extreme degree of leaky scanning, requiring the negotiation of 13 upstream AUGs. Ribosomal initiation complexes which fail to initiate at the E6 start codon can scan through to the E7 AUG without initiating translation, but competence to initiate is achieved once the E7 AUG is reached. These findings suggest that the E6 region of HPV-16 comprises features that sponsor both translation of the E6 protein and enhancement of translation at a downstream site.
Barbosa,
E2 of cottontail rabbit papillomavirus is a nuclear phosphoprotein translated from an mRNA encoding multiple open reading frames.
1988, Pubmed
Barbosa,
E2 of cottontail rabbit papillomavirus is a nuclear phosphoprotein translated from an mRNA encoding multiple open reading frames.
1988,
Pubmed
Biegalke,
Translational inhibition by cytomegalovirus transcript leaders.
1990,
Pubmed
Brown,
Virus-like particles and E1-E4 protein expressed from the human papillomavirus type 11 bicistronic E1-E4-L1 transcript.
1996,
Pubmed
Böhm,
The predominant mRNA class in HPV16-infected genital neoplasias does not encode the E6 or the E7 protein.
1993,
Pubmed
Cavener,
Eukaryotic start and stop translation sites.
1991,
Pubmed
Chiang,
An E1M--E2C fusion protein encoded by human papillomavirus type 11 is asequence-specific transcription repressor.
1991,
Pubmed
Chow,
Identification and mapping of human papillomavirus type 1 RNA transcripts recovered from plantar warts and infected epithelial cell cultures.
1987,
Pubmed
Chow,
Human papillomavirus types 6 and 11 mRNAs from genital condylomata acuminata.
1987,
Pubmed
Dolph,
Translation by the adenovirus tripartite leader: elements which determine independence from cap-binding protein complex.
1990,
Pubmed
Dominguez,
Ribosome shunting in cauliflower mosaic virus. Identification of an essential and sufficient structural element.
1998,
Pubmed
Doorbar,
Detection of novel splicing patterns in a HPV16-containing keratinocyte cell line.
1990,
Pubmed
Falcone,
Both the 5' untranslated region and the sequences surrounding the start site contribute to efficient initiation of translation in vitro.
1991,
Pubmed
,
Xenbase
Fuerst,
Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase.
1986,
Pubmed
Fütterer,
Nonlinear ribosome migration on cauliflower mosaic virus 35S RNA.
1993,
Pubmed
Grassmann,
Identification of a differentiation-inducible promoter in the E7 open reading frame of human papillomavirus type 16 (HPV-16) in raft cultures of a new cell line containing high copy numbers of episomal HPV-16 DNA.
1996,
Pubmed
Higgins,
Transcription patterns of human papillomavirus type 16 in genital intraepithelial neoplasia: evidence for promoter usage within the E7 open reading frame during epithelial differentiation.
1992,
Pubmed
Hummel,
Differentiation-induced and constitutive transcription of human papillomavirus type 31b in cell lines containing viral episomes.
1992,
Pubmed
Hummel,
Human papillomavirus type 31b late gene expression is regulated through protein kinase C-mediated changes in RNA processing.
1995,
Pubmed
Iftner,
The E7 protein of human papillomavirus 8 is a nonphosphorylated protein of 17 kDa and can be generated by two different mechanisms.
1990,
Pubmed
Jackson,
Potassium salts influence the fidelity of mRNA translation initiation in rabbit reticulocyte lysates: unique features of encephalomyocarditis virus RNA translation.
1991,
Pubmed
Jaeger,
Improved predictions of secondary structures for RNA.
1989,
Pubmed
Kozak,
How do eucaryotic ribosomes select initiation regions in messenger RNA?
1978,
Pubmed
Kozak,
Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes.
1986,
Pubmed
Kozak,
At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells.
1987,
Pubmed
Kozak,
Effects of intercistronic length on the efficiency of reinitiation by eucaryotic ribosomes.
1987,
Pubmed
Kozak,
A short leader sequence impairs the fidelity of initiation by eukaryotic ribosomes.
1991,
Pubmed
Kozak,
Regulation of translation in eukaryotic systems.
1992,
Pubmed
Kozak,
The scanning model for translation: an update.
1989,
Pubmed
Kozak,
Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs.
1989,
Pubmed
Lamphear,
Heat shock impairs the interaction of cap-binding protein complex with 5' mRNA cap.
1991,
Pubmed
Latorre,
Sendai virus Y proteins are initiated by a ribosomal shunt.
1998,
Pubmed
Lawson,
Influence of 5' proximal secondary structure on the translational efficiency of eukaryotic mRNAs and on their interaction with initiation factors.
1986,
Pubmed
Lingelbach,
An extended RNA/RNA duplex structure within the coding region of mRNA does not block translational elongation.
1988,
Pubmed
Luukkonen,
Efficiency of reinitiation of translation on human immunodeficiency virus type 1 mRNAs is determined by the length of the upstream open reading frame and by intercistronic distance.
1995,
Pubmed
Nasseri,
A human papilloma virus type 11 transcript encoding an E1--E4 protein.
1987,
Pubmed
Ozbun,
Two novel promoters in the upstream regulatory region of human papillomavirus type 31b are negatively regulated by epithelial differentiation.
1999,
Pubmed
Ozbun,
Characterization of late gene transcripts expressed during vegetative replication of human papillomavirus type 31b.
1997,
Pubmed
Ozbun,
Temporal usage of multiple promoters during the life cycle of human papillomavirus type 31b.
1998,
Pubmed
Palermo-Dilts,
Human papillomavirus type 1 produces redundant as well as polycistronic mRNAs in plantar warts.
1990,
Pubmed
Panniers,
The effect of Mg2+ and guanine nucleotide exchange factor on the binding of guanine nucleotides to eukaryotic initiation factor 2.
1988,
Pubmed
Panniers,
Translational control during heat shock.
1994,
Pubmed
Pelletier,
Insertion mutagenesis to increase secondary structure within the 5' noncoding region of a eukaryotic mRNA reduces translational efficiency.
1985,
Pubmed
Pim,
Alternatively spliced HPV-18 E6* protein inhibits E6 mediated degradation of p53 and suppresses transformed cell growth.
1997,
Pubmed
Remm,
Human papillomavirus type 18 E1 protein is translated from polycistronic mRNA by a discontinuous scanning mechanism.
1999,
Pubmed
Reynolds,
Unique features of internal initiation of hepatitis C virus RNA translation.
1995,
Pubmed
Roggenbuck,
Human papillomavirus type 18 E6*, E6, and E7 protein synthesis in cell-free translation systems and comparison of E6 and E7 in vitro translation products to proteins immunoprecipitated from human epithelial cells.
1991,
Pubmed
Rohlfs,
Viral transcription in human keratinocyte cell lines immortalized by human papillomavirus type-16.
1991,
Pubmed
Rosenberg,
Vectors for selective expression of cloned DNAs by T7 RNA polymerase.
1987,
Pubmed
Rotenberg,
Characterization of cDNAs of spliced HPV-11 E2 mRNA and other HPV mRNAs recovered via retrovirus-mediated gene transfer.
1989,
Pubmed
Rotenberg,
Characterization of rare human papillomavirus type 11 mRNAs coding for regulatory and structural proteins, using the polymerase chain reaction.
1989,
Pubmed
Schmidt-Puchta,
Plant ribosome shunting in vitro.
1997,
Pubmed
Schneider-Gädicke,
Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes.
1986,
Pubmed
Schärer-Hernández,
Nonlinear ribosome migration on cauliflower mosaic virus 35S RNA in transgenic tobacco plants.
1998,
Pubmed
Sedman,
The full-length E6 protein of human papillomavirus type 16 has transforming and trans-activating activities and cooperates with E7 to immortalize keratinocytes in culture.
1991,
Pubmed
Seedorf,
Human papillomavirus type 16 DNA sequence.
1985,
Pubmed
Sherman,
Expression and splicing patterns of human papillomavirus type-16 mRNAs in pre-cancerous lesions and carcinomas of the cervix, in human keratinocytes immortalized by HPV 16, and in cell lines established from cervical cancers.
1992,
Pubmed
Sherman,
Human papillomavirus type 16 expresses a variety of alternatively spliced mRNAs putatively encoding the E2 protein.
1992,
Pubmed
Slusher,
mRNA leader length and initiation codon context determine alternative AUG selection for the yeast gene MOD5.
1991,
Pubmed
Smotkin,
The major human papillomavirus protein in cervical cancers is a cytoplasmic phosphoprotein.
1987,
Pubmed
Smotkin,
Oncogenic and nononcogenic human genital papillomaviruses generate the E7 mRNA by different mechanisms.
1989,
Pubmed
Stacey,
Expression of human papillomavirus type 16 E7 protein by recombinant baculovirus and use for the detection of E7 antibodies in sera from cervical carcinoma patients.
1993,
Pubmed
Stacey,
Scanning the structure and antigenicity of HPV-16 E6 and E7 oncoproteins using antipeptide antibodies.
1994,
Pubmed
Stacey,
Translation of the human papillomavirus type 16 E7 oncoprotein from bicistronic mRNA is independent of splicing events within the E6 open reading frame.
1995,
Pubmed
Stoneley,
C-Myc 5' untranslated region contains an internal ribosome entry segment.
1998,
Pubmed
Tan,
Mechanism of translation of the bicistronic mRNA encoding human papillomavirus type 16 E6-E7 genes.
1994,
Pubmed
Yueh,
Selective translation initiation by ribosome jumping in adenovirus-infected and heat-shocked cells.
1996,
Pubmed
Zhang,
Secondary structure analysis of adenovirus tripartite leader.
1989,
Pubmed
Zuker,
On finding all suboptimal foldings of an RNA molecule.
1989,
Pubmed
