HyperTRIBE uncovers increased MUSASHI-2 RNA binding activity and differential regulation in leukemic stem cells
| Autor: | Yuheng Lu, Saroj Gourkanti, Ly P. Vu, Alexandra Schurer, Christina S. Leslie, Payal Patel, Diu T.T. Nguyen, Sun Mi Park, Ersilia Barin, Christopher R. Chin, Camila Prieto, Angela M. Savino, Zi-ning Choo, Michael G. Kharas, Karen L. Chu, Xuejing Yang |
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| Přispěvatelé: | 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 |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adenosine Deaminase General Physics and Astronomy RNA-binding protein RNA-Binding Protein Mice 0302 clinical medicine HEK293 Cell Gene expression Leukaemia Drosophila Proteins Gene Regulatory Networks RNA-Seq lcsh:Science Mice Knockout Regulation of gene expression Gene Regulatory Network Leukemia Multidisciplinary Cancer stem cells Gene Expression Regulation Leukemic Haematopoietic stem cells RNA-Binding Proteins Cell Differentiation Cell biology Haematopoiesis RNA editing 030220 oncology & carcinogenesis Neoplastic Stem Cells Self-renewal Stem cell Human endocrine system Recombinant Fusion Proteins Science Primary Cell Culture Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Animals Humans RNA Messenger Progenitor cell Binding Sites Animal Binding Site RNA Hematopoietic Stem Cell General Chemistry Hematopoietic Stem Cells Disease Models Animal HEK293 Cells 030104 developmental biology Drosophila Protein lcsh:Q Neoplastic Stem Cell |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. The identification of mRNA targets for RNA binding proteins (RBP) in stem cells is difficult due to the limited number of available cells. Here, as a proof-of-principle, the authors adapt the HyperTRIBE method to find that an RBP, MSI2, has increased RNA binding in leukemic compared with normal stem cells for selective regulation of oncogenic genes. |
| Databáze: | OpenAIRE |
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