Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells Academic Article uri icon

Overview

MeSH Major

  • Gene Expression Regulation, Leukemic
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Leukemia, Myeloid
  • RNA-Binding Proteins

abstract

  • The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis. Gene expression profiling of SYNCRIP-depleted cells demonstrated a loss of the MLL and HOXA9 leukemia stem cell program. SYNCRIP and MSI2 interact indirectly though shared mRNA targets. SYNCRIP maintains HOXA9 translation, and MSI2 or HOXA9 overexpression rescued the effects of SYNCRIP depletion. Altogether, our data identify SYNCRIP as a new RBP that controls the myeloid leukemia stem cell program. We propose that targeting these RBP complexes might provide a novel therapeutic strategy in leukemia.

authors

publication date

  • April 24, 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5508533

Digital Object Identifier (DOI)

  • 10.1038/ng.3854

PubMed ID

  • 28436985

Additional Document Info

start page

  • 866

end page

  • 875