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Updated: Jul 30, 2025

Using the E1A Minigene Tool to Study mRNA Splicing Changes
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Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

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Splicing Characterization and Isoform Switch Events in Human Keratinocytes Carrying Oncogenes from High-Risk HPV-16

Maryam Nasiri-Aghdam1,2, Mariel Garcia-Chagollan3, Ana Laura Pereira-Suarez4

  • 1División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico.

International Journal of Molecular Sciences
|May 13, 2023
PubMed

Insights

High-risk human papillomavirus (HR-HPV) oncogenes drive cervical cancer by altering mRNA processing. Low-risk HPV (LR-HPV) may counteract this, suggesting functional differences are key to cancer progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Virology

Background:

  • High-risk human papillomavirus (HR-HPV) infection promotes cervical cancer through oncogenic protein expression (E5, E6, E7), causing genomic instability.
  • Low-risk HPV (LR-HPV) may mitigate cancer progression, indicating functional differences between HPV types are crucial for understanding cervical cancer development.

Purpose of the Study:

  • To investigate the functional differences between LR-HPV and HR-HPV by analyzing transcriptome modulations induced by their respective oncogenes.
  • To identify specific mRNA processing alterations associated with HR-HPV oncogenes that distinguish cancer-progressing changes.

Main Methods:

  • Established HaCaT cells with constitutive expression of HPV-16 (HR-HPV) and HPV-84 (LR-HPV) oncogenes (E5, E6, E7) using lentiviral strategies.
  • Performed RNA sequencing (RNAseq) to analyze transcriptome-wide changes caused by individual oncogenes.

Main Results:

  • Identified significant alterations in RNA degradation, spliceosome, and RNA polymerase pathways related to mRNA processing in HPV-infected cells.
  • Observed distinct patterns of alternative transcription termination site (ATTS) usage and intron retention (IR) between HR-HPV and LR-HPV oncogene expression.
  • Detected differential expression of coding isoforms for genes like ADAM10, CLSPN, and RNPS1, favoring HR-HPV-associated changes.

Conclusions:

  • Highlighted significant differences in mRNA processing between LR-HPV and HR-HPV, particularly concerning alternative splicing and termination.
  • Identified key molecular events in mRNA processing that are crucial for cervical cancer development and progression, potentially differentiating the roles of LR-HPV and HR-HPV.
Keywords:
cervical cancerhigh-risk HPVlow-risk HPVmRNA processingsplicing

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