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Updated: May 26, 2026

Using the E1A Minigene Tool to Study mRNA Splicing Changes
Published on: April 22, 2021
Mammary gland selective excision of c-jun identifies its role in mRNA splicing
Sanjay Katiyar1, Xuanmao Jiao, Sankar Addya
1Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abstract:
The c-jun gene regulates cellular proliferation and apoptosis via direct regulation of cellular gene expression. Alternative splicing of pre-mRNA increases the diversity of protein functions, and alternate splicing events occur in tumors. Here, by targeting the excision of the endogenous c-jun gene within the mouse mammary epithelium, we have identified its selective role as an inhibitor of RNA splicing. Microarray-based assessment of gene expression, on laser capture microdissected c-jun(-/-) mammary epithelium, showed that endogenous c-jun regulates the expression of approximately 50 genes governing RNA splicing. In addition, genome-wide splicing arrays showed that endogenous c-jun regulated the alternate exon of approximately 147 genes, and 18% of these were either alternatively spliced in human tumors or involved in apoptosis. Endogenous c-jun also was shown to reduce splicing activity, which required the c-jun dimerization domain. Together, our findings suggest that c-jun directly attenuates RNA splicing efficiency, which may be of broad biologic importance as alternative splicing plays an important role in both cancer development and therapy resistance.
Insights
The c-jun gene acts as an inhibitor of RNA splicing, impacting cellular processes. This finding is crucial for understanding cancer development and therapy resistance.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Biology
Background:
- The c-jun gene regulates cellular proliferation and apoptosis through gene expression.
- Alternative splicing of pre-mRNA diversifies protein functions and is implicated in tumor development.
Purpose of the Study:
- To investigate the role of the endogenous c-jun gene in RNA splicing within the mouse mammary epithelium.
- To identify specific genes and pathways regulated by c-jun in the context of splicing.
Main Methods:
- Targeted excision of the endogenous c-jun gene in mouse mammary epithelium.
- Microarray-based gene expression analysis of c-jun(-/-) mammary epithelium.
- Genome-wide splicing array analysis.
Main Results:
- Endogenous c-jun was identified as a selective inhibitor of RNA splicing.
- Approximately 50 RNA splicing-governing genes were found to be regulated by endogenous c-jun.
- Endogenous c-jun regulated alternative exon splicing in approximately 147 genes, with 18% linked to human tumors or apoptosis.
- Reduced splicing activity was observed, dependent on the c-jun dimerization domain.
Conclusions:
- Endogenous c-jun directly attenuates RNA splicing efficiency.
- Alternative splicing's role in cancer development and therapy resistance highlights the biologic importance of these findings.
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