Human papillomavirus type 8 E7 protein binds nuclear myosin 1c and downregulates the expression of pre-rRNA

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• The role of beta human papillomaviruses (HPV) E6 and E7 oncogenes in skin cancer requires further investigation.
• Identifying cellular binding partners for these oncogenes is crucial for understanding their oncogenic mechanisms.

Purpose of the Study:

• To identify novel cellular binding partners for beta HPV E6 and E7 oncogenes.
• To investigate the functional consequences of the interaction between HPV 8 E7 and its binding partners on cellular processes, specifically ribosomal RNA (rRNA) synthesis.

Main Methods:

• Glutathione S-transferase (GST) pulldown assays to identify protein interactions.
• Coimmunoprecipitation to confirm binding partners.
• Analysis of RNA polymerase I activity and rRNA precursor and mature transcript levels.

Main Results:

• Nuclear myosin 1c was identified as a binding partner of the HPV 8 E7 protein.
• HPV 8 E7 expression led to decreased RNA polymerase I activity and reduced pre-ribosomal RNA (rRNA) synthesis.
• Despite reduced pre-rRNA, mature cytoplasmic 18S and 28S rRNA levels were maintained.

Conclusions:

• HPV 8 E7 interacts with nuclear myosin 1c, a component of the RNA polymerase I transcription complex.
• HPV 8 E7 downregulates rRNA transcription, potentially by inhibiting RNA polymerase I activity.
• This downregulation may redirect cellular resources to support efficient HPV replication in differentiating epithelial cells.