生物
RNA剪接
选择性拼接
拼接因子
病毒
细胞生物学
RNA结合蛋白
基因表达
细胞分化
基因
分子生物学
病毒学
信使核糖核酸
核糖核酸
遗传学
作者
Thanaporn Cheun-Im,Jingxin Zhang,Steven G. Milligan,Maria G. McPhillips,Sheila V. Graham
出处
期刊:Virus Research
[Elsevier]
日期:2008-02-01
卷期号:131 (2): 189-198
被引量:48
标识
DOI:10.1016/j.virusres.2007.09.006
摘要
Human papillomavirus type 16 (HPV16) infects anogenital epithelia and is the etiological agent of cervical cancer. We showed previously that HPV16 infection regulates the key splicing/alternative splicing factor SF2/ASF and that virus late transcripts are extensively alternatively spliced. hnRNP A1 is the antagonistic counterpart of SF2/ASF in alternative splicing. We show here that hnRNP A1 is also up-regulated during differentiation of virus-infected epithelial cells in monolayer and organotypic raft culture. Taken together with our previous data on SF2/ASF, this comprises the first report of HPV-mediated regulation of expression of two functionally related cellular proteins during epithelial differentiation. Further, using electrophoretic mobility shift assays and UV crosslinking we demonstrate that hnRNP A1 binds the HPV16 late regulatory element (LRE) in differentiated HPV16 infected cells. The LRE has been shown to be important in temporally controlling virus late gene expression during epithelial differentiation. We suggest that increased levels of these cellular RNA processing factors facilitate appropriate alternative splicing necessary for production of virus late transcripts in differentiated epithelial cells.
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