The HPV-16 E7 oncoprotein is expressed mainly from the unspliced E6/E7 transcript in cervical carcinoma C33-A cells.
The HPV-16 E6/E7 early transcripts are first produced as bicistronic or polycistronic mRNAs, and about 90% of the original pre-mRNA is spliced to produce three new alternative mRNAs. HPV-16 spliced transcripts are expressed heterogeneously in tumors and cell lines. Our results suggest that suboptimal splicing acceptor sites in E6/E7 intron 1 and the differential expression of splicing factors are involved in the production of the heterogeneous splicing profile in cell lines. The unspliced pre-mRNA and the alternative spliced transcripts contribute differentially to the production of E7 in stably transfected C33-A cells. The highest level of E7 was produced from the least prevalent transcript, the unspliced E6/E7(pre-mRNA). The order of relative expression of E7 was unspliced E6/E7(pre-mRNA) > E6*I/E7 > E6*II/E7. Our findings suggest that E6/E7 alternative splicing may be a mechanism for differential expression of the E6 and E7 oncoproteins, which also affects the expression of their targets, the proteins p53 and pRb.
del Moral-Hernández
Oscar
O
Unidad Zacatenco, Depto. Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados-IPN (CINVESTAV-IPN), Av. IPN # 2508, Zacatenco, Apdo. Postal 14-740, 07360, Mexico, D.F., Mexico.
López-Urrutia
Eduardo
E
Bonilla-Moreno
Raúl
R
Martínez-Salazar
Martha
M
Arechaga-Ocampo
Elena
E
Berumen
Jaime
J
Villegas-Sepúlveda
Nicolás
N
D045744:Cell Line, Tumor; D005260:Female; D015967:Gene Expression Regulation, Viral; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D050725:Papillomavirus E7 Proteins / Q000096:biosynthesis*; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D014158:Transcription, Genetic
D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; C059731:oncogene protein E7, Human papillomavirus type 16