Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells Journal Article
| Authors: | Vu, L. P.; Prieto, C.; Amin, E. M.; Chhangawala, S.; Krivtsov, A.; Calvo-Vidal, M. N.; Chou, T.; Chow, A.; Minuesa, G.; Park, S. M.; Barlowe, T. S.; Taggart, J.; Tivnan, P.; Deering, R. P.; Chu, L. P.; Kwon, J. A.; Meydan, C.; Perales-Paton, J.; Arshi, A.; Gönen, M.; Famulare, C.; Patel, M.; Paietta, E.; Tallman, M. S.; Lu, Y.; Glass, J.; Garret-Bakelman, F. E.; Melnick, A.; Levine, R.; Al-Shahrour, F.; Järås, M.; Hacohen, N.; Hwang, A.; Garippa, R.; Lengner, C. J.; Armstrong, S. A.; Cerchietti, L.; Cowley, G. S.; Root, D.; Doench, J.; Leslie, C.; Ebert, B. L.; Kharas, M. G. |
| Article Title: | Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells |
| 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. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved. |
| Keywords: | controlled study; protein expression; gene translocation; human cell; nonhuman; animal cell; animal tissue; gene; cell survival; apoptosis; gene expression; gene expression profiling; in vivo study; cell differentiation; in vitro study; proteomics; messenger rna; nucleic acid analysis; gene interaction; leukemogenesis; cancer stem cell; hematopoiesis; fetus; short hairpin rna; rna binding; myeloid leukemia; transcription factor hoxa9; mixed lineage leukemia protein; human; priority journal; article; myeloid leukemia cell line; crispr cas system; msi2 gene; syncrip gene |
| Journal Title: | Nature Genetics |
| Volume: | 49 |
| Issue: | 6 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-06-01 |
| Start Page: | 866 |
| End Page: | 875 |
| Language: | English |
| DOI: | 10.1038/ng.3854 |
| PROVIDER: | scopus |
| PUBMED: | 28436985 |
| PMCID: | PMC5508533 |
| DOI/URL: | |
| Notes: | Arshi Arora's first and last names are reversed on the original publication -- Article -- Export Date: 3 July 2017 -- Source: Scopus |
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