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The work also integrates emerging regulatory proteins and interprets how these events influence tumorigenic and antitumorigenic functions, informing mechanisms and potential clinical utility.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/alternative-splicing-in-the-genome-of-hpv-and-its-regulation-review/338401/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/alternative-splicing-in-the-genome-of-hpv-and-its-regulation-review/338401.png","ImageObject",300,407,{"name":42,"@type":43},"Eden","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is HR-HPV infection a major cause of cervical cancer?","Question",{"text":63,"@type":64},"HR-HPV persistent infections are linked to sustained expression of the E6 and E7 oncogenes and reduced expression of the L1 and L2 capsid proteins.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does alternative splicing contribute to HPV gene regulation?",{"text":68,"@type":64},"Alternative splicing of HPV pre-mRNAs generates multiple splice isoforms with distinct coding potentials, producing different proteins and altering expression of HPV genes.",{"name":70,"@type":61,"acceptedAnswer":71},"What is E6* and why is it important?",{"text":72,"@type":64},"E6* is a truncated E6-related splicing isoform derived from specific donor and acceptor splice site combinations within the E6 region. 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Cell. Infect. Microbiol. 14:1443868 .  \ndoi: 10.3389/fcimb.2024.1443868  \nCOPYRIGHT  \n© 2024 Wang, Chen, Qu, Gong, Wang, Chen, Zhou, Mo, Zhang, Lin, Bi, Wang, Gu, Li and Sui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nAlternative splicing in the genome of HPV and its regulation  \nYaping Wang 1,2†, Fang Chen 1†, Wenjie Qu 1,2, Yingxin Gong 1,2  \n,  \nYan Wang1, Limei Chen 1, Qi Zhou 1, Jiayin Mo 1,2,  \nHongwei Zhang 1, Lin Lin 1, Tianyi Bi 1,2, Xujie Wang3, Jiashi Gu 4, Yanyun Li 1,2* and Long Sui 1,2*  \n1 Department of Gynecology and Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China, 2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China, 3 Department of Obstetrics and Gynecology, Shanghai Changning Maternity and Infant Health Hospital, Shanghai, China, 4 Department of Obstetrics and Gynecology, Shanghai Pudong Hospital of Fudan University, Shanghai, China  \nPersistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. These chronic infections are characterized by high expression of the HPV E6 and E7 oncogenes and the absence of the L1 and L2 capsid proteins. The regulation of HPV gene expression plays a crucial role in both the viral life cycle and rare oncogenic events. Alternative splicing of HPV mRNA is a key mechanism in post-transcriptional regulation. Through alternative splicing, HPV mRNA is diversified into various splice isoforms with distinct coding potentials, encoding multiple proteins and influencing the expression of HPV genes. The spliced mRNAs derived from a donor splicing site within the E6 ORFand one of the different acceptor sites located in the early mRNA contain E6 truncated mRNAs, named E6* . E6* is one of the extensively studied splicing isoforms. However, the role of E6* proteins in cancer progression remains controversial. Here, we reviewed and compared the alternative splicing events occurring in the genomes of HR-HPV and LR-HPV. Recently, new HPV alternative splicing regulatory proteins have been continuously discovered, and we have updated the regulation of HPV alternative splicing. In addition, we summarized the functions of known splice isoforms from three aspects: antitumorigenic, tumorigenic, and other cancer-related functions, including not only E6*, but also E6^E7, E8^E2, and so on. Comprehending their contributions to cancer development enhances insights into the carcinogenic mechanisms of HPV and explores the potential utility of alternative splicing in the diagnosis and treatment of cervical cancer.  \nKEYWORDS  \nHPV, alternative splicing, splice sites, RBPs, splicing isoforms  \nFrontiers in Cellular and Infection Microbiology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nCervical canc","cbCaikTcRb63sqAw","https://ap.wps.com/l/cbCaikTcRb63sqAw","pdf",1348429,12,"English","# 1 Introduction\n## Persistent infection and cervical cancer context\n## HPV genome organization and regulatory regions\n## Infection stages and alternative splicing during the viral life cycle","[{\"question\":\"Why is HR-HPV infection a major cause of cervical cancer?\",\"answer\":\"HR-HPV persistent infections are linked to sustained expression of the E6 and E7 oncogenes and reduced expression of the L1 and L2 capsid proteins.\"},{\"question\":\"How does alternative splicing contribute to HPV gene regulation?\",\"answer\":\"Alternative splicing of HPV pre-mRNAs generates multiple splice isoforms with distinct coding potentials, producing different proteins and altering expression of HPV genes.\"},{\"question\":\"What is E6* and why is it important?\",\"answer\":\"E6* is a truncated E6-related splicing isoform derived from specific donor and acceptor splice site combinations within the E6 region. Its role in cancer progression is described as studied yet still controversial.\"}]","Alternative splicing in the genome of HPV and its regulation - Review | PDF",1790023485]