The Musashi1 (Msi1) gene identified in mouse is a member of a subfamily of RNA binding proteins that are highly
conserved across species.
Musashi1 (Msi1) is highly enriched in neural
precursor cells that are capable of generating both neurons and glia during embryonic
and postnatal CNS development.
NCBI Summary:
This gene encodes a protein containing two conserved tandem RNA recognition motifs. Similar proteins in other species function as RNA-binding proteins and play central roles in posttranscriptional gene regulation. Expression of this gene has been correlated with the grade of the malignancy and proliferative activity in gliomas and melanomas. A pseudogene for this gene is located on chromosome 11q13. [provided by RefSeq, Jul 2008]
General function
RNA binding, Translation factor
Comment
Musashi-directed translational activation of target mRNAs is mediated by the polyA] polymerase, Germline Development-2. [Cragle C 2014 et al.
The mRNA binding protein, Musashi, has been shown to regulate translation of select mRNAs and control cellular identity in both stem cells and cancer cells. Within mammalian cells, Musashi has traditionally been characterized as a repressor of translation. However, we have demonstrated that Musashi is an activator of translation in progesterone-stimulated oocytes of the frog Xenopus laevis, and recent evidence has revealed the capability of Musashi to function as an activator of translation in mammalian systems. The molecular mechanism by which Musashi directs activation of target mRNAs has not been elucidated. Here, we report a specific association of Musashi with the noncanonical poly[A] polymerase Germline Development-2 (GLD2) and map the association domain to 30 amino acids within the C-terminal domain of Musashi. We show that loss of GLD2 interaction through deletion of the binding domain, or treatment with antisense oligonucleotides compromises Musashi function. Additionally, we demonstrate that overexpression of both Musashi and GLD2 significantly enhances Musashi function. Finally, we report a similar co-association also occurs between murine Musashi and GLD2 orthologs, suggesting that coupling of Musashi to the polyadenylation apparatus is a conserved mechanism to promote target mRNA translation.
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Cellular localization
Cytoplasmic
Comment
Ovarian function
Follicle development
Comment
Knockout of RNA Binding Protein MSI2 Impairs Follicle Development in the Mouse Ovary: Characterization of MSI1 and MSI2 during Folliculogenesis. Sutherland JM et al. (2015) Characterizing the mechanisms underlying follicle development in the ovary is crucial to understanding female fertility and is an area of increasing research interest. The RNA binding protein Musashi is essential for post-transcriptional regulation of oocyte maturation in Xenopus and is expressed during ovarian development in Drosophila. In mammals Musashi is important for spermatogenesis and male fertility, but its role in the ovary has yet to be characterized. In this study we determined the expression of mammalian Musashi proteins MSI1 and MSI2 during mouse folliculogenesis, and through the use of a MSI2-specific knockout mouse model we identified that MSI2 is essential for normal follicle development. Time-course characterization of MSI1 and MSI2 revealed distinct differences in steady-state mRNA levels and protein expression/localization at important developmental time-points during folliculogenesis. Using a gene-trap mouse model that inactivates Msi2, we observed a significant decrease in ovarian mass, and change in follicle-stage composition due to developmental blocking of antral stage follicles and pre-antral follicle loss through atresia. We also confirmed that hormonally stimulated Msi2-deficient mice produce significantly fewer MII oocytes (60.9% less than controls, p < 0.05). Furthermore, the majority of these oocytes are of poor viability (62.2% non-viable/apoptotic, p < 0.05), which causes a reduction in female fertility evidenced by decreased litter size in Msi2-deficient animals (33.1% reduction to controls, p < 0.05). Our findings indicate that MSI1 and MSI2 display distinct expression profiles during mammalian folliculogenesis and that MSI2 is required for pre-antral follicle development.//////////////////
Efficient translation of dnmt1 requires cytoplasmic polyadenylation and musashi binding elements. Rutledge CE 2014 et al.
Regulation of DNMT1 is critical for epigenetic control of many genes and for genome stability. Using phylogenetic analysis we characterized a block of 27 nucleotides in the 3'UTR of Dnmt1 mRNA identical between humans and Xenopus and investigated the role of the individual elements contained within it. This region contains a cytoplasmic polyadenylation element (CPE) and a Musashi binding element (MBE), with CPE binding protein 1 (CPEB1) known to bind to the former in mouse oocytes. The presence of these elements usually indicates translational control by elongation and shortening of the poly(A) tail in the cytoplasm of the oocyte and in some somatic cell types. We demonstrate for the first time cytoplasmic polyadenylation of Dnmt1 during periods of oocyte growth in mouse and during oocyte activation in Xenopus. Furthermore we show by RNA immunoprecipitation that Musashi1 (MSI1) binds to the MBE and that this element is required for polyadenylation in oocytes. As well as a role in oocytes, site-directed mutagenesis and reporter assays confirm that mutation of either the MBE or CPE reduce DNMT1 translation in somatic cells, but likely act in the same pathway: deletion of the whole conserved region has more severe effects on translation in both ES and differentiated cells. In adult cells lacking MSI1 there is a greater dependency on the CPE, with depletion of CPEB1 or CPEB4 by RNAi resulting in substantially reduced levels of endogenous DNMT1 protein and concurrent upregulation of the well characterised CPEB target mRNA cyclin B1. Our findings demonstrate that CPE- and MBE-mediated translation regulate DNMT1 expression, representing a novel mechanism of post-transcriptional control for this gene.
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Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa
Comment
P.T.K. Saunders et al 2002 reported that
RNA Binding Protein Musashi1 Is Expressed in Sertoli
Cells in the Rat Testis from Fetal Life to Adulthood .
Msi1 expression is highly enriched in proliferative cells within the developing central nervous
system. In fetal and adult rat
ovaries, Msi1 was detected in granulosa cells and their precursors. In Sertoli cells, protein was detected in both
cytoplasmic and nuclear compartments; in adult testes, the immunointensity of the nuclear staining was stage dependent, with
highest levels of expression in Sertoli cells at stages IVI. In rat gonads, the RNA binding protein Msi1 is expressed in both
proliferating and nonproliferating Sertoli and granulosa cells.