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REVIEW article

Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Volume 14 - 2024 | doi: 10.3389/fcimb.2024.1443868
This article is part of the Research Topic Papillomaviruses, immunity, and tumour development View all 7 articles

Alternative Splicing in the Genomes of HPV and Its Regulation

Provisionally accepted
Yaping Wang Yaping Wang 1Fang Chen Fang Chen 1*Wenjie Qu Wenjie Qu 1Yingxin Gong Yingxin Gong 1*Wang Yan Wang Yan 1Limei Chen Limei Chen 1*Qi Zhou Qi Zhou 1*Jiayin Mo Jiayin Mo 1*Hongwei Zhang Hongwei Zhang 1*Lin Lin Lin Lin 1*Tianyi Bi Tianyi Bi 1Xujie Wang Xujie Wang 2Jiashi Gu Jiashi Gu 3*Yanyun Li Yanyun Li 1*Long Sui Long Sui 1*
  • 1 Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
  • 2 Shanghai Changning District Maternal and Child Health Hospital, Shanghai, China
  • 3 Department of Obstetrics and Gynecology, Shanghai Pudong Hospital, Shanghai, Shanghai Municipality, China

The final, formatted version of the article will be published soon.

    Persistent 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 ORF and 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.

    Keywords: HPV, Alternative Splicing, splice sites, RBPs, Splicing isoforms

    Received: 04 Jun 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Wang, Chen, Qu, Gong, Yan, 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) or licensor 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.

    * Correspondence:
    Fang Chen, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
    Yingxin Gong, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
    Limei Chen, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
    Qi Zhou, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
    Jiayin Mo, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
    Hongwei Zhang, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
    Lin Lin, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
    Jiashi Gu, Department of Obstetrics and Gynecology, Shanghai Pudong Hospital, Shanghai, 200032, Shanghai Municipality, China
    Yanyun Li, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
    Long Sui, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.