| 1989 |
Yeast MSI1 encodes a WD40-repeat protein that negatively regulates the RAS-cAMP signaling pathway; overexpression of MSI1 suppresses heat shock sensitivity and reduces elevated intracellular cAMP levels caused by ira1 or RAS2Val19 mutations, but not bcy1 mutations, placing MSI1 upstream of cAMP but downstream of (or parallel to) BCY1. |
Genetic suppression screen (high-copy plasmid suppressors of ira1 heat-shock sensitivity); cAMP measurement; sporulation assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
2554329
|
| 2001 |
CAC3/MSI1 suppression of the RAS/cAMP pathway is independent of chromatin assembly factor I (CAF-I) subunits CAC1 and CAC2. Cac3p/Msi1p localizes to both nucleus and cytoplasm and physically associates with Npr1p (a cytoplasmic kinase). Deletion of NPR1 phenocopies CAC3 overexpression in suppressing RAS/cAMP, and NPR1 overexpression blocks CAC3-mediated suppression, indicating that excess Cac3p suppresses RAS/cAMP by sequestering Npr1p. |
Genetic epistasis (double mutants), co-immunoprecipitation/association assay, localization studies, suppression analysis |
Molecular and cellular biology |
High |
11238915
|
| 2000 |
MSI1 overexpression suppresses hyperactive RAS phenotypes in multiple genetic backgrounds but does not inhibit cAMP synthesis or total cellular PKA activity. MSI1 requires the PKA regulatory subunit BCY1 to inhibit a mutationally activated PKA catalytic subunit, indicating that MSI1 modulates PKA function in a BCY1-dependent manner. MSI1's RAS-suppressing function is separable from its role in CAF-I chromatin assembly. |
Genetic analysis (multiple yeast strains, epistasis), PKA activity assay, cAMP measurement |
Current genetics |
Medium |
10975254
|
| 2007 |
MSI1 (CAC3) genetically interacts with YAK1 (a kinase antagonizing RAS/cAMP). MSI1 suppresses heat-shock sensitivity from yak1 deletion. YAK1 is required for Msi1p association with Cac1p (yeast two-hybrid). Msi1p can activate transcription of a reporter when tethered near a promoter in non-fermentable carbon conditions, and this activity requires YAK1. YAK1 antagonizes nuclear accumulation of Msi1p in non-fermenting cells. |
Yeast two-hybrid, genetic suppression, transcriptional reporter assay, localization analysis |
Journal of molecular biology |
Medium |
17321547
|
| 2006 |
Neural ELAV proteins (HuD) bind the AU-rich element (ARE) in the Msi1 mRNA 3'UTR in an ARE-dependent manner, stabilize the Msi1 ARE-containing mRNA in a deadenylation/degradation assay, and increase Musashi-1 protein levels. Activation of neural ELAV proteins by phorbol esters in SH-SY5Y cells increases Musashi-1 protein in the cytoskeleton. |
RNA-protein binding assay, mRNA deadenylation/degradation assay, immunofluorescence co-localization, pharmacological activation |
Journal of cell science |
Medium |
16554442
|
| 2014 |
MSI1 directly binds the 3'UTR of p21, p27, and p53 mRNAs (verified by RNA-protein binding assays) and suppresses their translation (confirmed by luciferase 3'UTR reporter assays). Overexpression of Msi1 in cervical cancer cells downregulates p21, p27, and p53 protein levels and promotes cell cycle S-phase entry, whereas shRNA knockdown upregulates these proteins and slows S-phase entry. |
RNA-protein binding assay, luciferase 3'UTR reporter assay, shRNA knockdown, Western blot, flow cytometry |
Oncotarget |
High |
25362645
|
| 2014 |
Msi1 directly suppresses translation of p21cip1 mRNA via its 3'UTR-specific motif, as demonstrated by a chimeric luciferase-p21cip1 3'UTR reporter assay. Knockdown of Msi1 in colon cancer cells increases p21cip1 protein, induces G0/G1 arrest, and suppresses proliferation and tumorsphere formation. |
Luciferase chimeric mRNA 3'UTR reporter assay, RNAi knockdown, Western blot, flow cytometry, in vivo xenograft |
International journal of oncology |
Medium |
25394506
|
| 2017 |
Msi1 promotes epithelial-to-mesenchymal transition (EMT) in cervical cancer cells; shRNA silencing of Msi1 reduces EMT marker expression and inhibits Wnt signaling activity, while Msi1 expression positively correlates with EMT markers in clinical tissues. |
shRNA knockdown, Western blot, invasion/migration assay, in vivo tumor assay, immunohistochemistry |
Human pathology |
Medium |
28088346
|
| 2017 |
MSI1 knockdown in osteosarcoma cells causes G0/G1 cell cycle arrest and upregulation of p21 and p27 protein levels. Luciferase assays confirm that MSI1 binds the 3'UTR of both p21 and p27 mRNAs. |
shRNA knockdown, luciferase 3'UTR reporter assay, Western blot, flow cytometry, in vivo xenograft |
Oncology letters |
Medium |
29113163
|
| 2015 |
Msi1 confers TRAIL resistance in hepatocellular carcinoma cells by activating ERK; forced Msi1 expression increases ERK activation and TRAIL resistance, and siRNA depletion of ERK overcomes Msi1-mediated TRAIL resistance. Differential AKT activation was not responsible. |
Stable subline isolation, shRNA/siRNA knockdown, forced expression, TRAIL resistance assays in vitro and in vivo xenograft |
FEBS letters |
Medium |
25747387
|
| 2018 |
MSI1 enhances GBM radioresistance by increasing homologous recombination (HR) DNA repair and promoting VCAM1-mediated tumor invasion; MSI1 knockdown causes DNA damage accumulation in irradiated GBM cells and reduces xenograft tumor formation after irradiation. |
shRNA knockdown, overexpression, irradiation assays, DNA damage markers (γH2AX), invasion assay, xenograft |
Radiotherapy and oncology |
Medium |
30322656
|
| 2020 |
The Msi1-mTOR pathway drives keratinocyte-to-Paget-like cell conversion; Msi1 overexpression in epidermal basal cells activates mTOR signaling, and mTOR inhibition with rapamycin rescues the Paget-like phenotype in Msi1-overexpressing transgenic mice. |
Transgenic mouse model, single-cell RNA-sequencing, lineage tracing, rapamycin treatment, RNA velocity analysis |
Cell research |
High |
32457396
|
| 2020 |
MSI1 promotes breast cancer metastasis by directly suppressing TIMP3 mRNA (an endogenous inhibitor of MMP9), leading to increased MMP9 expression and activity, invadopodia formation, and ECM degradation. The MSI1-TIMP3-MMP9 cascade is required for invadopodia-mediated metastasis. |
shRNA knockdown, overexpression, RNA-binding assay (direct suppression of Timp3), MMP9 activity assay, invadopodia assay, in vivo lung metastasis model, clinical correlation |
Oncogene |
High |
34155343
|
| 2020 |
MSI1 promotes expression of the GBM stem cell marker CD44 by impairing miRNA-dependent degradation of CD44 mRNA via its 3'UTR; this regulation is disrupted by the MSI1 inhibitor luteolin. |
Knockdown and overexpression, 3'UTR reporter assay, mRNA turnover assay, luteolin inhibitor treatment, GBM cell and primary tumorsphere models |
Cancers |
Medium |
33291443
|
| 2020 |
MSI1 directly binds and stabilizes the Fthl17c mRNA; MSI1 ablation in mESCs reduces Fthl17c expression, decreasing intracellular Fe2⁺, impairing TET enzyme activity, and increasing global DNA methylation (5mC). FTHL17C interacts with TET1 in the nucleus. Restoration of Fthl17c rescues TET activity and pluripotency gene expression, defining an MSI1-FTHL17C-Fe2⁺-TET axis linking post-transcriptional iron homeostasis control with epigenetic remodeling. |
Genetic ablation (MSI1 knockout), RNA immunoprecipitation, biochemical TET activity assay, DNA methylation (5mC) measurement, co-immunoprecipitation (FTHL17C-TET1), rescue experiments, fluorescence imaging |
Cell regeneration (London, England) |
Medium |
42089935
|
| 2021 |
MSI1 interacts with AGO2 via its C-terminus; peptides mimicking the C-terminus of MSI1 (Pep#11 and Pep#26) competitively interfere with MSI1-AGO2 binding (confirmed by Biacore binding analyses), reduce GBM tumorigenesis, and improve survival in GBM animal models. |
Peptide array, Biacore surface plasmon resonance, recombinant reporter system, in vivo GBM xenograft model |
Cancers |
Medium |
35158774
|
| 2021 |
MSI1 inhibits cervical cancer cell apoptosis by downregulating PTEN, thereby activating AKT signaling, which reduces the proapoptotic protein BAK; rescue of BAK expression in Msi1-expressing cells restores apoptosis. |
Overexpression, shRNA knockdown, Western blot, apoptosis assay, rescue experiment (BAK re-expression), in vivo xenograft |
Journal of Cancer |
Medium |
33758618
|
| 2022 |
MSI1 phosphorylation at residues T18, S19, and S34 (identified by mass spectrometry in C. elegans MSI-1) is necessary for MSI-1 function in both short- and long-term aversive olfactory associative memory; CRISPR-based manipulation of these phosphorylation sites abolishes memory-related MSI-1 function. MSI-1 function is controlled by activity rather than expression levels. |
Mass spectrometry phosphorylation mapping, CRISPR-based point mutations, behavioral assays (short- and long-term memory) |
PLoS genetics |
Medium |
36223338
|
| 2020 |
In photoreceptor neurons, both MSI1 and MSI2 are required for inclusion of photoreceptor-specific alternative exons in transcripts critical for outer segment morphogenesis (Cc2d2a, Cep290, Prom1, Ttc8), ciliogenesis, and synaptic transmission. Loss of both Msi1 and Msi2 causes disrupted outer segment morphology, ciliary defects, loss of light response, and photoreceptor degeneration within 6 months. |
Conditional double knockout mouse (pan-retinal and rod-specific), electrophysiology (ERG), RNA splicing analysis, immunofluorescence, histology |
The Journal of biological chemistry |
High |
33168629
|
| 2025 |
A single Musashi allele (from either Msi1 or Msi2) is sufficient to maintain photoreceptor function and high inclusion levels of photoreceptor-specific alternative exons (in Cc2d2a, Cep290, Prom1, Ttc8), demonstrating that the Musashi proteins act in a dose-dependent, partially redundant manner to regulate alternative splicing specifically in photoreceptors. |
Combined conditional Msi1/Msi2 knockouts with progressive allele reduction, RT-PCR splicing analysis, electrophysiology |
bioRxivpreprint |
Medium |
bio_10.1101_2025.11.26.690869
|
| 2024 |
MSI1 directly binds the SARS-CoV-2 3'UTR (confirmed by in vivo RNA immunoprecipitation and biochemical assays), and this binding results in translational repression mediated by inhibition of Poly(A)-binding protein (PABP). MSI1 knockout promotes robust viral replication and increased viral protein expression in intestinal cells, stem cells, and 3D organoids. |
Computational prediction, RNA immunoprecipitation (RIP), biochemical binding assay, MSI1 knockout cell lines, 2D and 3D organoid infection assays, viral protein expression quantification |
bioRxivpreprint |
Medium |
bio_10.1101_2024.09.29.615653
|
| 2013 |
Hedgehog signaling agonist (purmorphamine) enhances mesenchymal stem cell proliferation and suppresses apoptosis through the RNA-binding protein Msi1, which regulates c-Myc oncoprotein expression and p21CIP1 cell cycle regulator, and modulates miRNA-148a and miRNA-148b. |
Hedgehog agonist/antagonist treatment, MSI1 knockdown/overexpression, Western blot, proliferation and apoptosis assays |
PloS one |
Low |
23418578
|
| 2013 |
Hedgehog signaling negatively regulates osteogenic differentiation of mesenchymal stem cells through Msi1, which suppresses Wnt1 expression and the miR-148 family (especially miR-148b). |
Hedgehog agonist/antagonist treatment, Msi1 knockdown/overexpression, osteogenic differentiation assays, qRT-PCR |
Bone |
Low |
23880227
|
| 2025 |
MSI1 binds to the ABHD2 promoter region and activates ABHD2 transcription (confirmed by dual-luciferase reporter and ChIP assays), thereby promoting prostate cancer cell proliferation, migration, and glycolysis. |
ChIP assay, dual-luciferase reporter assay, siRNA knockdown, EdU proliferation assay, flow cytometry, transwell assay, glycolysis measurement, xenograft |
Biochemical genetics |
Medium |
40067652
|
| 2022 |
MSI1 binds MACF1 mRNA (confirmed by RNA immunoprecipitation) and stabilizes MACF1 expression. MSI1 and MACF1 both increase in high-glucose-induced MC3T3-E1 cells; MSI1-mediated effects on proliferation, apoptosis inhibition, and osteogenic differentiation require MACF1. The MSI1-MACF1 axis suppresses Wnt/β-catenin signaling to promote osteogenic differentiation. |
RNA immunoprecipitation (RIP), siRNA knockdown, Western blot, CCK-8 assay, TUNEL assay, ALP activity, alizarin red staining |
Molecular biotechnology |
Low |
36443618
|