Ask about this productRelated genes to: MSI2 Blocking Peptide
- Gene:
- MSI2 NIH gene
- Name:
- musashi RNA binding protein 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 17q22
- Locus Type:
- gene with protein product
- Date approved:
- 2002-04-29
- Date modifiied:
- 2016-10-24
Related products to: MSI2 Blocking Peptide
Related articles to: MSI2 Blocking Peptide
- To investigate the role and molecular mechanisms of the RNA-binding protein MATR3 in myocardial fibrosis of atrial fibrillation (AF). Expression of MATR3 and MSI2 in AF patients was analyzed using GEO datasets (GSE79768, GSE14975, GSE31821). Human atrial fibroblasts (HAFs) induced by Angiotensin II (Ang-II) were used as an in vitro cellular model of myocardial fibrosis. Expression and interactions of MATR3, METTL3, and MSI2 were validated by qRT-PCR and Western blot. The binding between MATR3 and METTL3 was confirmed by co-immunoprecipitation (Co-IP). The mA modification level of MSI2 mRNA was detected by methylated RNA immunoprecipitation (MeRIP-qPCR). Cell proliferation, migration, and fibrotic phenotypes were evaluated by CCK-8, EdU, scratch, and Transwell assays, as well as detection of fibrosis markers. An Ang-II-induced mouse model of atrial fibrosis was constructed, and the in vivo effects of MATR3 were verified by HE staining, Masson's trichrome staining, and molecular detection. Analysis of GEO datasets showed that both MATR3 and MSI2 were highly expressed in AF patients. Ang-II treatment significantly upregulated the expression of MATR3 in HAFs, while knockdown of MATR3 inhibited Ang-II-induced proliferation, migration, and pro-fibrotic phenotypic changes in HAFs (reducing the expression of α-SMA, collagen I/III). Mechanistically, MATR3 interacted endogenously with METTL3 and stabilized the METTL3 protein by inhibiting proteasomal degradation. METTL3 mediated the mA modification of MSI2 mRNA, enhancing its stability and promoting its expression. MSI2 exerted a pro-fibrotic effect by activating the Wnt/β-Catenin pathway. In vivo experiments confirmed that silencing MATR3 downregulated the expression of METTL3 and MSI2, inhibited the activation of the Wnt pathway, and alleviated Ang-II-induced atrial fibrosis in mice. MATR3 promotes myocardial fibrosis and exacerbates AF by regulating METTL3-mediated mA modification of MSI2 mRNA to activate the Wnt/β-Catenin pathway. Targeting MATR3 may represent a potential therapeutic strategy for AF. - Source: PubMed
Publication date: 2026/03/18
Wei ZihanLi JingDai PinjiQian ChengLi Xiaoli - Clonal hematopoiesis of indeterminate potential (CHIP) is a precursor condition characterized by the expansion of blood cell clones harboring somatic mutations originating in hematopoietic stem cells (HSCs). Since individuals with CHIP face a high risk of developing myeloid malignancies, targeting CHIP clones could provide a viable strategy for leukemia prevention. Despite its clinical significance, the mechanisms underlying CHIP predisposition and progression remain poorly understood. Recent genome wide association studies (GWAS) have identified several non-coding genetic loci that are strongly associated with CHIP; however, their underlying mechanisms still remain unknown. We hypothesize that risk variants in these non-coding loci modulate enhancer elements active in HSCs. To test this, we selected 1,374 non-coding variants from 51 loci associated for CHIP risk in the UK Biobank and screened them for regulatory activity using a Massively Parallel Reporter Assay (MPRA). We performed our lentiviral MPRA screen in MUTZ-3 cells, a human hematopoietic cell line relevant to HSCs, which express CD34 surface marker and are dependent on HSC-specific transcription factors. Using a MPRA library of ~73,000 constructs in CD34+ fraction of MUTZ-3 cells, we identified 87 variants representing 32 GWAS loci. We used targeted genome editing to demonstrate endogenous enhancer activity across 3 MPRA variants that affect the transcription of NKD2, FLT3, and MSI2. Our functional studies on MSI2 indicate that presence of higher levels of MSI2 mediated by CHIP risk allele enhances the clonal expansion of TET2 knockout hematopoietic stem and progenitor cells, providing a mechanistic link whereby non-coding genetic variants can influence the expansion of mutant CHIP clones. - Source: PubMed
Publication date: 2026/01/23
Nguyen TrieuJeejan JessicaIwasaki TakeshiKales SusanChakraborty JoyeetaYanase ChieShekhar ArunaKwasniak DominikaHegde AditiVoit RichardStengel KristyIto KeisukeTewhey RyanNandakumar Satish - Increasing evidence shows that RNA-binding proteins play crucial roles in modulating the blood-tumor barrier (BTB) permeability in glioblastoma (GB). In this study, we identified elevated expression of Musashi RNA-binding protein 2 (MSI2) and Long intergenic nonprotein coding RNA 667 (LINC00667) in glioma co-cultured endothelial cells. MSI2 enhanced the stability of LINC00667, and its knockdown elevated the BTB permeability. In contrast, transcription factor interferon regulatory factor 6 (IRF6) exhibited reduced expression in glioma co-cultured endothelial cells, and its over-expression elevated the BTB permeability. Mechanistically, LINC00667 facilitated IRF6 mRNA degradation through Staufen1-mediated mRNA decay pathway. IRF6 inhibited the transcriptions of key tight junction associated proteins (ZO-1, occludin, and claudin-5) through promoter binding. That is, MSI2 knockdown down-regulated the expression of LINC00667, thereby diminishing its ability to degrade IRF6 through the Staufen1-mediated mRNA decay pathway. This led to IRF6 accumulation, which transcriptionally suppressed ZO-1, occludin and claudin-5 expression, ultimately increasing BTB permeability. Furthermore, both individual and combined modulation of MSI2 knockdown, LINC00667 knockdown and IRF6 over-expression enhanced BTB permeability to doxorubicin, thereby increasing the apoptosis rate of GB cells. Collectively, the MSI2/LINC00667/IRF6 pathway plays an important role in modulating BTB permeability, offering potential targets for new molecular therapies in GB. - Source: PubMed
Publication date: 2026/01/23
Gao RuiRuan XueleiXue YixueWang PingWang DiE TiangeLiu XiaobaiLiu Libo - Musashi 2 (MSI2), a conserved RNA-binding protein, is important in mammalian sperm and follicle development. Its function in Mongolian sheep, however, remains unclear. We investigated the differential expression of MSI2 in single and double dominant follicles of Mongolian sheep and its role in prolificacy. Sixty 7-month-old Mongolian ewes in estrus were studied. The results showed that MSI2 was expressed in Mongolian sheep ovarian granulosa cells, and the mRNA and protein expression levels of MSI2 were significantly higher in single dominant follicles than in double dominant follicles. There were 3400 DEGs in the single and double dominant follicles of Mongolian sheep, which were mainly enriched in steroidogenesis, TGF-β, and estrogen signaling pathways; based on PPI analysis, further studies were conducted on CYP17A1, ERβ, StAR, and 3β-HSD that interact with MSI2. It has been confirmed that they are coexpressed in Mongolian sheep ovarian granulosa cells. The mRNA and protein expression levels of MSI2 and CYP17A1 in double dominant follicles were significantly lower than those in single dominant follicles, with a significant positive correlation. In contrast, 3β-HSD, StAR, and ERβ were more highly expressed in double follicles, correlating negatively with MSI2. It is speculated that reduced expression of MSI2 and CYP17A1 in double dominant follicles promotes the expression of StAR, 3β-HSD, and ERβ, thereby facilitating the formation of double dominant follicles in Mongolian sheep. This study confirms that MSI2 may serve as an essential regulatory factor for Mongolian sheep multiparity trait, providing a theoretical basis for further research on the trait. - Source: PubMed
Publication date: 2026/01/15
Qinqin HaoPenghui LiXin ZhouYang HeHaodong LiuXiaolong LiMingyang YuZelin ZhangJiaxin FanWenchao YangJunzhe YinGuifang CaoHaijun LiXiaojuan CaoHaiyan GeYongqiang LiJunguang RenChenguang Du - Myeloid leukemias, diseases marked by aggressiveness and poor outcomes, are frequently triggered by oncogenic translocations. In the case of chronic myelogenous leukemia (CML), the BCR-ABL fusion initiates chronic phase disease with second hits allowing progression to blast crisis. Although Gleevec has been transformative for CML, blast crisis CML remains relatively drug resistant. Here, we show that , a translocation with an unknown role in cancer, can serve as a second hit in driving bcCML. Compared to BCR-ABL, BCR-ABL/MSI2-HOXA9 led to a more aggressive disease in vivo with decreased latency, increased lethality, and a differentiation blockade that is a hallmark of blast crisis. Domain mapping revealed that the RNA binding domain RRM1 had a preferential impact on growth and lethality of bcCML relative to RRM2 or the HOXA9 domain. Mechanistically, MSI2-HOXA9 triggered global downstream changes with a preferential upregulation of mitochondrial components. Consistent with this, BCR-ABL/MSI2-HOXA9 cells exhibited a significant increase in mitochondrial respiration. These data suggest that MSI2-HOXA9 acts, at least in part, by increasing expression of the mitochondrial polymerase POLRMT and augmenting mitochondrial function and basal respiration in blast crisis. Collectively, our findings demonstrate for the first time that translocations involving the stem and developmental signal MSI2 can be oncogenic and suggest that MSI, which we found to be a frequent partner for an array of translocations, could also be a driver mutation across solid cancers. - Source: PubMed
Publication date: 2026/01/07
Spinler KyleHamilton MichaelBajaj JeevishaShima YutakaDiaz EmilyKritzik MarcieReya Tannishtha