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Updated: Jul 3, 2025

Using the E1A Minigene Tool to Study mRNA Splicing Changes
Published on: April 22, 2021
RNA elements that control human papillomavirus mRNA splicing-targets for therapy?
Stefan Schwartz1, Chengjun Wu2, Naoko Kajitani1
1Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Abstract:
Human papillomaviruses (HPVs) cause more than 4.5% of all cancer in the world and more than half of these cases are attributed to human papillomavirus type 16 (HPV16). Prophylactic vaccines are available but antiviral drugs are not. Novel targets for therapy are urgently needed. Alternative RNA splicing is extensively used by HPVs to express all their genes and HPV16 is no exception. This process must function to perfection since mis-splicing could perturb the HPV gene expression program by altering mRNA levels or by generating dysfunctional mRNAs. Cis-acting RNA elements on the viral mRNAs and their cognate cellular trans-acting factors control papillomavirus RNA splicing. The precise but delicate nature of the splicing process renders splicing sensitive to interference. As such, papillomavirus RNA splicing is a potential target for therapy. Here we summarize our current understanding of cis-acting HPV16 RNA elements that control HPV16 mRNA splicing via cellular proteins and discuss how they may be exploited as targets for therapy to papillomavirus infections and cancer.
Insights
Human papillomaviruses (HPVs), particularly HPV16, cause significant global cancer burdens. Targeting HPV16 RNA splicing offers a novel therapeutic strategy against these infections and associated cancers.
Area of Science:
- Virology
- Molecular Biology
- Oncology
Background:
- Human papillomaviruses (HPVs) are responsible for over 4.5% of global cancers, with HPV type 16 (HPV16) implicated in more than half of these cases.
- While prophylactic vaccines exist, effective antiviral drugs for HPV infections are lacking, necessitating the urgent identification of novel therapeutic targets.
- Alternative RNA splicing is a critical mechanism for gene expression in HPVs, including HPV16, and precise regulation is essential for viral function.
Purpose of the Study:
- To summarize the current understanding of cis-acting RNA elements in HPV16 that regulate viral mRNA splicing.
- To discuss the role of cellular trans-acting factors interacting with these RNA elements.
- To explore the potential of exploiting HPV16 RNA splicing as a therapeutic target for HPV infections and cancer.
Main Methods:
- Review and synthesis of existing research on HPV16 RNA splicing mechanisms.
- Analysis of cis-acting RNA elements within HPV16 mRNAs.
- Investigation of interactions between viral RNA elements and cellular splicing factors.
Main Results:
- HPV16 extensively utilizes alternative RNA splicing for its gene expression.
- Specific cis-acting RNA elements on HPV16 mRNAs, in conjunction with cellular proteins, precisely control the splicing process.
- Disruptions in this delicate splicing mechanism can lead to altered mRNA levels or dysfunctional viral transcripts.
Conclusions:
- Papillomavirus RNA splicing is a sensitive process, making it a viable target for therapeutic intervention.
- Understanding the interplay between HPV16 cis-acting RNA elements and cellular factors is key to developing novel antiviral strategies.
- Targeting HPV16 RNA splicing presents a promising avenue for treating HPV-associated cancers and infections.
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