HyperTRIBE uncovers increased MUSASHI-2 RNA binding activity and differential regulation in leukemic stem cells Journal Article

Authors: Nguyen, D. T. T.; Lu, Y.; Chu, K. L.; Yang, X.; Park, S. M.; Choo, Z. N.; Chin, C. R.; Prieto, C.; Schurer, A.; Barin, E.; Savino, A. M.; Gourkanti, S.; Patel, P.; Vu, L. P.; Leslie, C. S.; Kharas, M. G.
Article Title: HyperTRIBE uncovers increased MUSASHI-2 RNA binding activity and differential regulation in leukemic stem cells
Abstract: The cell-context dependency for RNA binding proteins (RBPs) mediated control of stem cell fate remains to be defined. Here we adapt the HyperTRIBE method using an RBP fused to a Drosophila RNA editing enzyme (ADAR) to globally map the mRNA targets of the RBP MSI2 in mammalian adult normal and malignant stem cells. We reveal a unique MUSASHI-2 (MSI2) mRNA binding network in hematopoietic stem cells that changes during transition to multipotent progenitors. Additionally, we discover a significant increase in RNA binding activity of MSI2 in leukemic stem cells compared with normal hematopoietic stem and progenitor cells, resulting in selective regulation of MSI2’s oncogenic targets. This provides a basis for MSI2 increased dependency in leukemia cells compared to normal cells. Moreover, our study provides a way to measure RBP function in rare cells and suggests that RBPs can achieve differential binding activity during cell state transition independent of gene expression. © 2020, The Author(s).
Keywords: signal transduction; controlled study; leukemia; unclassified drug; gene mutation; human cell; nonhuman; flow cytometry; binding affinity; animal cell; mouse; mammalia; animal tissue; gene expression; animal experiment; protein; cell differentiation; enzyme activity; rna binding protein; rna; genetic transfection; leukemogenesis; cancer stem cell; immunoprecipitation; hematopoiesis; gene silencing; bioinformatics; transcriptome; rna splicing; rna extraction; rna sequence; enzyme; dna methyltransferase 3a; gene ontology; rna editing; sanger sequencing; cell component; cancer; human; article; luciferase assay; real time reverse transcription polymerase chain reaction; interleukin enhancer binding factor 3; musashi binding protein
Journal Title: Nature Communications
Volume: 11
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2020-04-24
Start Page: 2026
Language: English
DOI: 10.1038/s41467-020-15814-8
PUBMED: 32332729
PROVIDER: scopus
PMCID: PMC7181745
Notes: Article -- Export Date: 1 June 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Christina Leslie
    156 Leslie
  2. Michael Kharas
    71 Kharas
  3. Sun Mi Park
    18 Park
  4. Yuheng Lu
    17 Lu
  5. Camila Prieto
    8 Prieto
  6. Diu Thi Thanh Nguyen
    8 Nguyen
  7. Karen Chu
    3 Chu
  8. Alexandra Schurer
    10 Schurer
  9. Ersilia Barin
    5 Barin
  10. Angela Maria Savino
    5 Savino
  11. Xuejing Yang
    4 Yang