PRMT1 Modulates Alternative Splicing to Enhance HPV18 mRNA Stability and Promote the Establishment of Infection

Area of Science:

• Virology
• Molecular Biology
• Cancer Research

Background:

• Persistent human papillomavirus (HPV) infections are a primary cause of cervical cancer.
• Understanding the virus-host interactions that enable HPV establishment is crucial for developing therapeutic strategies.
• Temporal regulation of viral gene expression, particularly RNA splicing and polyadenylation, is key to the HPV lifecycle but remains incompletely understood.

Purpose of the Study:

• To identify cellular factors involved in the early stages of HPV infection and establishment.
• To investigate the role of protein arginine N-methyltransferase 1 (PRMT1) in the HPV lifecycle.
• To elucidate the molecular mechanisms by which PRMT1 influences HPV18 infection.

Main Methods:

• Utilized a single-cell genomics approach to screen for host factors critical for HPV infection.
• Analyzed HPV18-infected primary human cervical cells to assess PRMT1 expression and function.
• Investigated the impact of PRMT1 inhibition on viral RNA splicing, transcript stability, and gene expression.

Main Results:

• Identified PRMT1 as a critical host factor essential for HPV18 infection establishment in primary cells.
• Demonstrated that HPV18 infection increases PRMT1 levels throughout its lifecycle.
• Showed PRMT1 inhibition disrupts viral RNA splicing, causing intron retention, altered E6/E7 expression, and transcript degradation via nonsense-mediated decay (NMD).

Conclusions:

• PRMT1 is a key regulator of the HPV18 lifecycle, particularly impacting viral RNA processing.
• PRMT1 activity is essential for maintaining viral transcript stability and appropriate gene expression.
• PRMT1 represents a potential therapeutic target for managing persistent HPV18 infections and associated cancers.