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 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2020 -- Source: Scopus |
