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.

Nguyen, D., Lu, Y., Chu, K., Yang, X., Park, S., Choo, Z., et al. (2020). HyperTRIBE uncovers increased MUSASHI-2 RNA binding activity and differential regulation in leukemic stem cells. NATURE COMMUNICATIONS, 11(1) [10.1038/s41467-020-15814-8].

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

Savino, Angela M;
2020

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.
Si
Articolo in rivista - Articolo scientifico
Scientifica
Adenosine Deaminase; Animals; Binding Sites; Cell Differentiation; Disease Models, Animal; Drosophila Proteins; Gene Expression Regulation, Leukemic; Gene Regulatory Networks; HEK293 Cells; Hematopoietic Stem Cells; Humans; Leukemia; Mice; Mice, Knockout; Neoplastic Stem Cells; Primary Cell Culture; RNA, Messenger; RNA-Binding Proteins; RNA-Seq; Recombinant Fusion Proteins
English
Nguyen, D., Lu, Y., Chu, K., Yang, X., Park, S., Choo, Z., et al. (2020). HyperTRIBE uncovers increased MUSASHI-2 RNA binding activity and differential regulation in leukemic stem cells. NATURE COMMUNICATIONS, 11(1) [10.1038/s41467-020-15814-8].
Nguyen, D; Lu, Y; Chu, K; Yang, X; Park, S; Choo, Z; Chin, C; Prieto, C; Schurer, A; Barin, E; Savino, A; Gourkanti, S; Patel, P; Vu, L; Leslie, C; Kharas, M
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/391391
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