Köstler Wolfgang J, Zeisel Amit, Körner Cindy, Tsai Jonathan M, Jacob-Hirsch Jasmine, Ben-Chetrit Nir, Sharma Kirti, Cohen-Dvashi Hadas, Yitzhaky Assif, Lader Eric, Tschulena Ulrich, Rechavi Gideon, Domany Eytan, Wiemann Stefan, Yarden Yosef
Departments of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
PLoS One. 2013 Dec 6;8(12):e80566. doi: 10.1371/journal.pone.0080566. eCollection 2013.
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.
信号诱导的转录本异构体变异（TIV）包括替代启动子的使用以及mRNA的可变剪接和可变聚腺苷酸化。为了评估信号诱导的TIV的表型相关性，我们使用了外显子阵列和乳腺上皮细胞，这些细胞会响应表皮生长因子（EGF）而迁移。我们发现，EGF在一小时内就能迅速在相当一部分转录组中诱导广泛的TIV。重要的是，TIV表征了许多在刺激后没有差异表达的基因。此外，一组乳腺细胞系也有类似的EGF依赖性变化。一项利用异构体特异性siRNA寡核苷酸的功能筛选表明，几种异构体在EGF诱导的乳腺细胞迁移中发挥着重要的、非冗余的作用。综上所述，我们的研究结果突出了TIV在细胞对细胞外信号表型反应的快速演变中的重要性。
