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: © 2013 Köstler et al.
Köstler, W. J., Zeisel, A., Körner, C., Tsai, J. M., Jacob-Hirsch, J., Ben-Chetrit, N., … Yarden, Y. (2013). Epidermal growth-factor - Induced transcript isoform variation drives mammary cell migration. PLoS ONE, 8(12). https://doi.org/10.1371/journal.pone.0080566