来自杂志 Journal of Virology 的文献。
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龙海晨
(2022-07-02 20:10):
#paper Zheng Y, Jönsson J, Hao C, et al. hnRNP A1 and hnRNP A2 inhibit splicing to HPV16 splice site SA409 through a UAG-containing sequence in the E7 coding region[J]. Journal of Virology, 2020. DOI: 10.1128/jvi.01509-20 PMID: 32759322 PMCID: PMC7527060 该文章研究发现hnRNP A1和hnRNP A2通过E7编码区中含有UAG的序列抑制HPV16剪接位点SA409的剪接。人乳头瘤病毒16型(HPV16)属于HPV的高危型,并导致多种肛门,生殖器癌和头颈癌,一般大家最熟悉的就是宫颈癌,实际上高危型HPV可以引发多种癌症。HPV16的两种蛋白E6和E7可防止细胞凋亡并促进有丝分裂,对HPV16生命周期的完成、感染细胞的转化和恶性肿瘤的维持至关重要。E6和E7由两个通过选择性剪接以互斥方式生成的mRNA产生。虽然E6蛋白是由未拼接的mRNA制成的,但E7是由相同前体mRNA的拼接版本制成的。由于恶性转化需要足够数量的E6和E7,这种复杂的基因表达排列使得E6和E7的表达容易受到外部干扰。由于没有针对HPV16的抗病毒药物,详细了解HPV16 E6和E7 mRNA剪接的调节可能会发现新的治疗靶点。文章可总结为:1. E6,E7是HPV的重要蛋白他们对HPV的繁殖至关重要同时可以改变宿主的基因导致癌症。 2. E6,E7由HPV的同一段基因上的位点来调控。 3. 受到hnRNA1或者hnRNA2的调节,位点会做出不同反应从而影响E6或者E7的产生。hnRNP A1和A2对E6编码区这个非常脆弱的HPV16剪接事件有相反的影响。 4. hnrnpa1和A2对hpv16mrna剪接的影响差异主要是由于这两种蛋白的C端保守程度较低。结果还表明,hnRNP A2与其他下游RNA序列相互作用,以促进剪接到下游的3′-剪接SA742,而不是导致内含子保留在E6编码区。
Abstract:
Human papillomavirus type 16 (HPV16) belongs to the high-risk-group of HPVs and is causing a variety of anogenital cancers and head and neck cancer. The two HPV16 oncoproteins E6 and …
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Human papillomavirus type 16 (HPV16) belongs to the high-risk-group of HPVs and is causing a variety of anogenital cancers and head and neck cancer. The two HPV16 oncoproteins E6 and E7 prevent apoptosis and promote mitosis and are essential for completion of the HPV16 life cycle and for transformation of the infected cell and maintenance of malignancy. E6 and E7 are produced from two mRNAs that are generated in a mutually exclusive manner by alternative splicing. While E6 protein is made from the unspliced mRNA, E7 is made from the spliced version of the same pre-mRNA. Since sufficient quantities of both E6 and E7 are required for malignant transformation, this intricate arrangement of gene expression renders E6 and E7 expression vulnerable to external interference. Since antiviral drugs to HPV16 are not available, a detailed knowledge of the regulation of HPV16 E6 and E7 mRNA splicing may uncover novel targets for therapy.
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