TY - JOUR
T1 - Mammary gland selective excision of c-Jun identifies its role in mRNA splicing
AU - Katiyar, Sanjay
AU - Jiao, Xuanmao
AU - Addya, Sankar
AU - Ertel, Adam
AU - Covarrubias, Yolanda
AU - Rose, Vanessa
AU - Casimiro, Mathew C.
AU - Zhou, Jie
AU - Lisanti, Michael P.
AU - Nasim, Talat
AU - Fortina, Paolo
AU - Pestell, Richard G.
PY - 2012/2/15
Y1 - 2012/2/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84863152361&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-11-3647
DO - 10.1158/0008-5472.CAN-11-3647
M3 - Article
C2 - 22174367
AN - SCOPUS:84863152361
SN - 0008-5472
VL - 72
SP - 1023
EP - 1034
JO - Cancer Research
JF - Cancer Research
IS - 4
ER -