Control of the Papillomavirus Early-to-Late Switch by Differentially Expressed SRp20
Control of the Papillomavirus Early-to-Late Switch by Differentially Expressed SRp20
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DOI：
10.1128/jvi.01719-08
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发表时间：
2009-01-01
影响因子：
5.4
通讯作者：
Zheng, Zhi-Ming
中科院分区：
文献类型：
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作者：
Jia, Rong;Liu, Xuefeng;Zheng, Zhi-Ming
乳头瘤病毒感染的病毒早到晚转换与角化细胞分化密切相关，部分由可选择的mRNA剪接介导。在这里，我们报道了SRp20，一种细胞剪接因子，通过与富含a / c的RNA元件的相互作用来控制早到晚的开关。富含A/ c的SE4元件调控牛乳头瘤病毒1型（BPV-1）晚期特异性剪接位点的选择，而SRp20与SE4的结合抑制了这种选择。晚期BPV-1 L1或人乳头瘤病毒（HPV） L1（主要的衣壳蛋白）的表达与终末分化的角化细胞中SRp20水平呈负相关。在16型HPV中，一个类似的srp20相互作用元件也控制着病毒的早到晚转换。筏式培养的角质细胞支持L1表达，与不支持L1表达的单层培养的角质细胞相比，筏式培养的角质细胞产生的SRp20要少得多。相反，癌细胞或未分化角质形成细胞中丰富的SRp20通过促进细胞转录因子SP1的表达来反激活病毒早期启动子，对病毒早期E6和E7的表达很重要。
The viral early-to-late switch of papillomavirus infection is tightly linked to keratinocyte differentiation and is mediated in part by alternative mRNA splicing. Here, we report that SRp20, a cellular splicing factor, controls the early-to-late switch via interactions with A/C-rich RNA elements. An A/C-rich SE4 element regulates the selection of a bovine papillomavirus type 1 (BPV-1) late-specific splice site, and binding of SRp20 to SE4 suppresses this selection. Expression of late BPV-1 L1 or human papillomavirus (HPV) L1, the major capsid protein, inversely correlates with SRp20 levels in the terminally differentiated keratinocytes. In HPV type 16, a similar SRp20-interacting element also controls the viral early-to-late switch. Keratinocytes in raft cultures, which support L1 expression, make considerably less SRp20 than keratinocytes in monolayer cultures, which do not support L1 expression. Conversely, abundant SRp20 in cancer cells or undifferentiated keratinocytes is important for the expression of the viral early E6 and E7 by promoting the expression of cellular transcription factor SP1 for transactivation of viral early promoters.