The HPV-16 E7 oncoprotein is expressed mainly from the unspliced E6/E7 transcript in cervical carcinoma C33-A cells
The HPV-16 E7 oncoprotein is expressed mainly from the unspliced E6/E7 transcript in cervical carcinoma C33-A cells
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DOI：
10.1007/s00705-010-0787-9
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发表时间：
2010-12-01
影响因子：
2.7
通讯作者：
Villegas-Sepulveda, Nicolas
中科院分区：
文献类型：
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作者：
del Moral-Hernandez, Oscar;Lopez-Urrutia, Eduardo;Villegas-Sepulveda, Nicolas
HPV-16 E6/E7早期转录本首先作为双反子或多反子mrna产生，大约90%的原始pre-mRNA被剪接产生三种新的替代mrna。HPV-16剪接转录物在肿瘤和细胞系中表达异质性。我们的研究结果表明，E6/E7内含子1的次优剪接受体位点和剪接因子的差异表达参与了细胞系中异质剪接谱的产生。在稳定转染的C33-A细胞中，未剪接的pre-mRNA和可选择的剪接转录物对E7的产生有不同的贡献。最高水平的E7产生于最不普遍的转录物，即未剪接的E6/E7（pre-mRNA）。E7的相对表达顺序为未剪接的E6/E7(pre-mRNA) > E6*I/E7 > E6*II/E7。我们的研究结果表明，E6/E7选择性剪接可能是E6和E7癌蛋白差异表达的一种机制，这也影响了它们的靶蛋白p53和pRb的表达。
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.