TY - JOUR
T1 - Epidermal growth-factor - Induced transcript isoform variation drives mammary cell migration
AU - Köstler, Wolfgang J.
AU - Zeisel, Amit
AU - Körner, Cindy
AU - Tsai, Jonathan M.
AU - Jacob-Hirsch, Jasmine
AU - Ben-Chetrit, Nir
AU - Sharma, Kirti
AU - Cohen-Dvashi, Hadas
AU - Yitzhaky, Assif
AU - Lader, Eric
AU - Tschulena, Ulrich
AU - Rechavi, Gideon
AU - Domany, Eytan
AU - Wiemann, Stefan
AU - Yarden, Yosef
PY - 2013/12/6
Y1 - 2013/12/6
N2 - Signal-induced transcript isoform variation (TIV) includes alternative promoter usage as well as alternative splicing and alternative polyadenylation of mRNA. To assess the phenotypic relevance of signal-induced TIV, we employed exon arrays and breast epithelial cells, which migrate in response to the epidermal growth factor (EGF). We show that EGF rapidly - within one hour - induces widespread TIV in a significant fraction of the transcriptome. Importantly, TIV characterizes many genes that display no differential expression upon stimulus. In addition, similar EGF-dependent changes are shared by a panel of mammary cell lines. A functional screen, which utilized isoform-specific siRNA oligonucleotides, indicated that several isoforms play essential, non-redundant roles in EGF-induced mammary cell migration. Taken together, our findings highlight the importance of TIV in the rapid evolvement of a phenotypic response to extracellular signals. Copyright:
AB - Signal-induced transcript isoform variation (TIV) includes alternative promoter usage as well as alternative splicing and alternative polyadenylation of mRNA. To assess the phenotypic relevance of signal-induced TIV, we employed exon arrays and breast epithelial cells, which migrate in response to the epidermal growth factor (EGF). We show that EGF rapidly - within one hour - induces widespread TIV in a significant fraction of the transcriptome. Importantly, TIV characterizes many genes that display no differential expression upon stimulus. In addition, similar EGF-dependent changes are shared by a panel of mammary cell lines. A functional screen, which utilized isoform-specific siRNA oligonucleotides, indicated that several isoforms play essential, non-redundant roles in EGF-induced mammary cell migration. Taken together, our findings highlight the importance of TIV in the rapid evolvement of a phenotypic response to extracellular signals. Copyright:
UR - http://www.scopus.com/inward/record.url?scp=84891942332&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0080566
DO - 10.1371/journal.pone.0080566
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AN - SCOPUS:84891942332
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e80566
ER -