TY - JOUR T1 - Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state JF - bioRxiv DO - 10.1101/006270 SP - 006270 AU - Yarden Katz AU - Feifei Li AU - Nicole Lambert AU - Ethan Sokol AU - Wai-Leong Tam AU - Albert W. Cheng AU - Edoardo M. Airoldi AU - Christopher J. Lengner AU - Piyush B. Gupta AU - Zhengquan Yu AU - Rudolf Jaenisch AU - Christopher B. Burge Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/06/12/006270.abstract N2 - Summary The conserved Musashi (Msi) family of RNA binding proteins are expressed in stem/progenitor and cancer cells, but mostly absent from differentiated cells, consistent with a role in cell state regulation. We found that Msi genes are rarely mutated but frequently overexpressed in human cancers, and associated with an epithelial-luminal cell state. Using ribosome footprint profiling and RNA-seq analysis of genetic mouse models in neuronal and mammary cell types, we found that Msis regulate translation of genes implicated in epithelial cell biology and epithelial-to-mesenchymal transition (EMT) and promote an epithelial splicing pattern. Overexpression of Msi proteins inhibited translation of genes required for EMT, including Jagged1, and repressed EMT in cell culture and in mammary gland in vivo, while knockdown in epithelial cancer cells led to loss of epithelial identity. Our results show that mammalian Msi proteins contribute to an epithelial gene expression program and promote an epithelial-luminal state in both neural and breast cell types.Msi proteins bind UAG motifs in vitro and in 3’ UTRs of mRNAsMsi proteins are markers of epithelial state in brain and breast tumors, and cell linesThe Notch regulator Jag1 mRNA is bound and translationally repressed by MsiMsi overexpression represses EMT in the mammary gland in vivo ER -