Mammary gland selective excision of c-Jun identifies its role in mRNA splicing

Sanjay Katiyar, Xuanmao Jiao, Sankar Addya, Adam Ertel, Yolanda Covarrubias, Vanessa Rose, Mathew C. Casimiro, Jie Zhou, Michael P. Lisanti, Talat Nasim, Paolo Fortina, Richard G. Pestell

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1023-1034
Number of pages12
JournalCancer Research
Volume72
Issue number4
DOIs
Publication statusPublished - 15 Feb 2012
Externally publishedYes

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