Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state
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Burge_Musashi proteins.pdf
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Author(s)
Katz, Yarden
Li, Feifei
Lambert, Nicole J.
Tam, Wai-Leong
Airoldi, Edoardo M.
Lengner, Christopher J.
Yu, Zhengquan
Jaenisch, Rudolf
Sokol, Ethan Samuel
Cheng, Albert W.
Date Issued
November 2014
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Katz, Yarden, Feifei Li, Nicole J Lambert, Ethan S Sokol, Wai-Leong Tam, Albert W Cheng, Edoardo M Airoldi, et al. “Musashi Proteins Are Post-Transcriptional Regulators of the Epithelial-Luminal Cell State.” eLife 3 (November 7, 2014).
Version
Final published version
Abstract
The conserved Musashi (Msi) family of RNA binding proteins are expressed in stem/progenitor and cancer cells, but generally 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 are associated with an epithelial-luminal cell state. Using ribosome profiling and RNA-seq analysis, we found that Msi proteins 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 the translation of Jagged1, a factor required for EMT, and repressed EMT in cell culture and in mammary gland in vivo. Knockdown of Msis in epithelial cancer cells promoted loss of epithelial identity. Our results show that mammalian Msi proteins contribute to an epithelial gene expression program in neural and mammary cell types.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.7554/eLife.03915
