Small molecule inhibition of multiple RNA binding proteins underlies Musashi-2 independent phenotypes
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PROVIDER: PRJNA879765 | ENA |
REPOSITORIES: ENA
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Project description:RNA binding proteins (RBPs) are key regulators of normal and pathological gene expression. Small molecules targeting RBP-RNA interactions are a rapidly emerging class of therapeutics. Ro-08-2750 (Ro) was previously identified as a competitive inhibitor of Musashi-RNA interactions. Here we show Ro potently inhibits steroidogenesis and viability independent of Musashi-2 in multiple cell lines. We identified Ro-interacting proteins using an unbiased proteome-wide approach. Other RBPs were a prominent class of Ro-interacting proteins and leveraging large-scale ENCODE data we found a subset of these phenocopy Ro inhibition. We provide a general framework for validating the specificity and identifying targets of RBP inhibitors in a cellular context.
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Project description:mRNA-seq and ribosome profiling of neural stem cells overexpressing or knocked out for Musashi RNA-binding proteins
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Project description:Analysis of testis-specific over-expression of Musashi-1 and Musashi-2 at gene expression level. The hypothesis tested in the present study was that testis-specific over-expression of Musashi-1/Musashi-2 would result in differential gene expression profiles from the Wildtype control. Results provide important information of the genes affected by Musashi-2 overexpression during spermatogenesis.
2014-07-12 | GSE59358 | GEO
Project description:Analysis of testis-specific over-expression of Musashi-1 and Musashi-2 at gene expression level. The hypothesis tested in the present study was that testis-specific over-expression of Musashi-1/Musashi-2 would result in differential gene expression profiles from the Wildtype control. Results provide important information of the genes affected by Musashi-2 overexpression during spermatogenesis. Total RNA obtained from whole adult testis of transgenic testis-specfic Musashi-1 and Musashi-2 overexpression mice compared to Wildtype (control) littermates. 4 replicates, 16 samples, 2 comparisons: Wt (Musashi-1) vs. TgMsi1 & Wt (Musashi-2) vs. TgMsi2
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Project description:This SuperSeries is composed of the following subset Series: GSE16432: MSI2 regulates hematopoiesis and accelerates leukemogenesis GSE22773: Musashi 2 regulates normal hematopoiesis and accelerates leukemogenesis (LK and MS12-inducible) GSE22774: Musashi 2 regulates normal hematopoiesis and accelerates leukemogenesis (LSK and LK) GSE22775: Musashi 2 regulates normal hematopoiesis and accelerates leukemogenesis (Leukemia cell lines) Refer to individual Series
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Project description:mRNA-seq and ribosome profiling of neural stem cells overexpressing or knocked out for Musashi RNA-binding proteins Study of the global effects of Musashi (Msi) proteins on the transcriptome of embryonic neural stem cells. Neural stem cells were derived from brains of E12.5 or E13.5 embryos engineered to have inducible Msi1 or Msi2 genes, or from embryos with double floxed alleles of Msi1 and Msi2 carrying a Tamoxifen-induclble Cre (CreER). The overexpression mice were made using the Flp-in system (OpenBioSystems), where a cDNA of interest (in this case Msi1 or Msi2) is knocked into the Collagen (Col1A1) locus. The expression of the cDNA of interest is driven by m2rTTA that is knocked into the Rosa26 locus (R26). KH2 describes a strain containing the R26-m2rTTA but lacking Msi1 or Msi2 cDNA. MSI1 describes a strain containing R26-m2rTTA and Msi1 cDNA in Col1A1. MSI2 describes a strain containing R26-m2rTTA and Msi2 cDNA in Col1A1. C1 describes a strain lacking the CreER allele but containing double floxed alleles of Msi1/Msi2 (used as Tamoxifen control). C4 describes a strain carrying the CreER allele and double floxed alleles of Msi1/Msi2.
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Project description:The anterior pituitary is comprised of distinct cell types that each secrete specific hormones to control a variety of biological processes including growth, metabolism, reproduction and stress responses. The anterior pituitary shows a remarkable level of cell type plasticity that allows shifts in hormone producing populations to meet organismal demands. Pituitary cell plasticity is tightly regulated and both deficiency in cell plasticity and excessive cell plasticity are associated with common pituitary pathologies. The molecular mechanisms underlying this plasticity are not well characterized but recent work has implicated the stem cell determinants and sequence-specific mRNA binding proteins of the Musashi family as regulators of adult pituitary hormone production. In this study we have sought to identify the full range of Musashi target mRNAs in the adult mouse pituitary. Using Musashi RNA immunoprecipitation we identify a cohort of 1192 mRNAs that show specific Musashi binding. These include mRNAs restricted to discrete hormone-producing cell lineages as well as mRNAs associated with stem and progenitor cells. The processes influenced by the proteins encoded by the Musashi-associated mRNAs include cellular homeostasis, protein trafficking and secretion, unfolded protein response, endocrine processes and female pregnancy. Functional analysis of validated mRNA regulatory 3' untranslated regions (3’ UTRs) reveals UTR-specific positive or negative control by the Musashi proteins within the same cellular context. Together, our findings indicate a broad role for Musashi proteins in the control of pituitary function.
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Project description:Deciphering the mechanism of secondary cell wall/SCW formation in vascular plants is key to understanding their development and the molecular basis of biomass recalcitrance. Although a sophisticated network of transcription factors has been implicated in SCW synthesis in plants, little is known about the implication of RNA-binding proteins in this process. Here we report that two RNA-binding proteins homologous to the animal translational regulator Musashi, Musashi-Like2/MSIL2 and Musashi-Like4/MSIL4, function redundantly to control SCW formation in interfascicular fibers and the setting of biomass recalcitrance. We show that the disruption of MSIL2/4 (msil2-4 mutant) decreases the abundance of lignin in fibers and triggers an hypermethylation of glucuronoxylan that is linked to an over-accumulation of GlucuronoXylan Methyltransferase1/3 (GXM1/3) proteins.
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Project description:Transcripts regulated by Musashi-1 (MSI1) are explored through shRNA-mediated knockdown of MSI1 in SU_MB002 medulloblastoma cells.
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