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

Autor:	Nguyen DTT; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Lu Y; Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Blavatnik Institute of System Biology, Harvard Medical School, Boston, MA, 02115, USA., Chu EL; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.; Weill Cornell School of Medical Sciences, New York, NY, 10065, USA., Yang X; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Park SM; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Choo ZN; Weill Cornell School of Medical Sciences, New York, NY, 10065, USA., Chin CR; Weill Cornell School of Medical Sciences, New York, NY, 10065, USA., Prieto C; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Schurer A; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Barin E; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Savino AM; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Gourkanti S; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA., Patel P; Weill Cornell School of Medical Sciences, New York, NY, 10065, USA., Vu LP; Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.; Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, BC, V5A 1S6, Canada., Leslie CS; Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Kharas MG; Molecular Pharmacology Program, Center for Cell Engineering, Center for Stem Cell Biology, Center for Experimental Therapeutics, Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. kharasm@mskcc.org.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Apr 24; Vol. 11 (1), pp. 2026. Date of Electronic Publication: 2020 Apr 24.
DOI:	10.1038/s41467-020-15814-8
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu