1. Cancer Biology
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Musashi proteins are post-transcriptional regulators of the epithelial-luminal cell state

  1. Yarden Katz
  2. Feifei Li
  3. Nicole J Lambert
  4. Ethan S Sokol
  5. Wai Leong Tam
  6. Albert W Cheng
  7. Edoardo M Airoldi
  8. Christopher J Lengner
  9. Piyush B Gupta
  10. Zhengquan Yu
  11. Rudolf Jaenisch
  12. Christopher B Burge  Is a corresponding author
  1. Massachusetts Institute of Technology, United States
  2. China Agricultural University, China
  3. Whitehead Institute for Biomedical Research, United States
  4. Harvard University, United States
  5. University of Pennsylvania, United States
Research Article
  • Cited 62
  • Views 4,864
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Cite this article as: eLife 2014;3:e03915 doi: 10.7554/eLife.03915

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 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 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.

Article and author information

Author details

  1. Yarden Katz

    Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    No competing interests declared.
  2. Feifei Li

    China Agricultural University, Beijing, China
    Competing interests
    No competing interests declared.
  3. Nicole J Lambert

    Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Ethan S Sokol

    Whitehead Institute for Biomedical Research, Cambridge, United States
    Competing interests
    No competing interests declared.
  5. Wai Leong Tam

    Whitehead Institute for Biomedical Research, Cambridge, United States
    Competing interests
    No competing interests declared.
  6. Albert W Cheng

    Whitehead Institute for Biomedical Research, Cambridge, United States
    Competing interests
    No competing interests declared.
  7. Edoardo M Airoldi

    Harvard University, Cambridge, United States
    Competing interests
    Edoardo M Airoldi, Reviewing Editor, eLife.
  8. Christopher J Lengner

    University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  9. Piyush B Gupta

    Whitehead Institute for Biomedical Research, Cambridge, United States
    Competing interests
    No competing interests declared.
  10. Zhengquan Yu

    China Agricultural University, Beijing, China
    Competing interests
    No competing interests declared.
  11. Rudolf Jaenisch

    Whitehead Institute for Biomedical Research, Cambridge, United States
    Competing interests
    No competing interests declared.
  12. Christopher B Burge

    Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    cburge@mit.edu
    Competing interests
    No competing interests declared.

Ethics

Animal experimentation: Mice of the 129SvJae strain were used, and the K14-rTTA strain were obtained from JAX (stock number: 007678). Animal care was performed in accordance with institutional guidelines and approved by the Committee on Animal Care, Department of Comparative Medicine, Massachusetts Institute of Technology, under animal protocol 1013-088-16

Reviewing Editor

  1. Benjamin J Blencowe, University of Toronto, Canada

Publication history

  1. Received: July 6, 2014
  2. Accepted: November 5, 2014
  3. Accepted Manuscript published: November 7, 2014 (version 1)
  4. Version of Record published: December 15, 2014 (version 2)

Copyright

© 2014, Katz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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