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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- 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
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
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