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.

Cancer Research
|December 17, 2011
PubMed

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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