Systems Biology of RNA Binding Proteins

Thomas W Bebee, Benjamin W Cieply, Russ P Carstens, Thomas W. Bebee, Benjamin W. Cieply, Russ P. Carstens, Bebee, Thomas W., Cieply, Benjamin W., Carstens, Russ P.

Gene W. Yeo

The epithelial to mesenchymal transition (EMT) and reverse mesenchymal to epithelial transition (MET) are developmentally conserved processes that are essential for patterning of developing embryos and organs. The EMT/MET are further utilized in wound healing, but they can also be hijacked by cancer cells to promote tumor progression and metastasis. The molecular pathways governing these processes have historically focused on the transcriptional regulation and networks that control them. Indeed, global profiling of transcriptional changes has provided a wealth of information into how these networks are regulated, the downstream targets, and functional consequence of alterations to the global transcriptome. However, recent evidence has revealed that the posttranscriptional landscape of the cell is also dramatically altered during the EMT/MET and contributes to changes in cell behavior and phenotypes. While studies of this aspect of EMT biology are still in their infancy, recent progress has been achieved by the identification of several RNA binding proteins (RBPs) that regulate splicing, polyadenylation, mRNA stability, and translational control during EMT. This chapter focuses on the global impact of RBPs that regulate mRNA maturation as well as outlines the functional impact of several key posttranscriptional changes during the EMT. The growing evidence of RBP involvement in the cellular transformation during EMT underscores that a coordinated regulation of both transcriptional and posttranscriptional changes is essential for EMT. Furthermore, new discoveries into these events will paint a more detailed picture of the transcriptome during the EMT/MET and provide novel molecular targets for treatment of human diseases.