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RNA binding proteins in spermatogenesis: an in depth focus on the Musashi family.

Sutherland JM, Siddall NA, Hime GR, McLaughlin EA - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted.We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis.This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.

View Article: PubMed Central - PubMed

Affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.

ABSTRACT
Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactive transcription despite heavy translational requirements for continued growth and differentiation. Hence, spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation of gene expression, facilitated by RNA binding proteins (RBPs), which remain abundantly expressed throughout this process. One such group of proteins is the Musashi family, previously identified as critical regulators of testis germ cell development and meiosis in Drosophila, and also shown to be vital to sperm development and reproductive potential in the mouse. This review describes the role and function of RBPs within the scope of male germ cell development, focusing on our recent knowledge of the Musashi proteins in spermatogenesis. The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted. We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis. This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.

No MeSH data available.


Related in: MedlinePlus

Musashi RBP expression during spermatogenesis. dMsi paralogs dMsi and Rbp6 are differentially expressed in the fly testis: dMsi is nuclear and expressed in early germ cells and spermatocytes while Rbp6 is cytoplasmic and localized to spermatogonial cyst cells. Mammalian Msi1 is expressed in the cytoplasm of early mitotic germ cells before translocating to the nucleus upon transition to meiosis. Mammalian Msi2 is entirely nuclear, expressed throughout meiosis and during spermatid differentiation. The dotted line refers to cytoplasmic localization while the solid line refers to nuclear-specific expression. RBP: RNA binding proteins; Msi1: Musashi-1; Msi2: Musashi-2; dMsi: Drosophila Musashi; Rbp6: RNA-binding protein 6.
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Figure 3: Musashi RBP expression during spermatogenesis. dMsi paralogs dMsi and Rbp6 are differentially expressed in the fly testis: dMsi is nuclear and expressed in early germ cells and spermatocytes while Rbp6 is cytoplasmic and localized to spermatogonial cyst cells. Mammalian Msi1 is expressed in the cytoplasm of early mitotic germ cells before translocating to the nucleus upon transition to meiosis. Mammalian Msi2 is entirely nuclear, expressed throughout meiosis and during spermatid differentiation. The dotted line refers to cytoplasmic localization while the solid line refers to nuclear-specific expression. RBP: RNA binding proteins; Msi1: Musashi-1; Msi2: Musashi-2; dMsi: Drosophila Musashi; Rbp6: RNA-binding protein 6.

Mentions: Recent work has by our group detailed the distinctive expression of mammalian Msi1 and Msi2 and explored the outcomes of aberrant expression of both RBPs during the process of male gamete development.100 The unique spatial and temporal expression patterns of the Musashi proteins throughout spermatogenesis indicate individual roles of both RBPs throughout during gamete development in the mammalian testis (Figure 3). Specifically, Msi1 predominately localizes to the cytoplasmic compartments of mitotic gonocytes and spermatogonia, while Msi2 shows nuclear expression in meiotic spermatocytes and differentiating spermatids. The two novel transgenic mouse models utilized, with germ cell-specific overexpression of full-length isoforms of Msi1 or Msi2, demonstrated that aberrant expression of either gene was deleterious to normal spermatogenesis and detrimental to cell health. In addition to this, preliminary studies performed on human testicular seminoma tumors have provided further insights into the relevance of Msi1 and Msi2 over-expression as diagnostic markers to human stem cell cancers.100


RNA binding proteins in spermatogenesis: an in depth focus on the Musashi family.

Sutherland JM, Siddall NA, Hime GR, McLaughlin EA - Asian J. Androl. (2015 Jul-Aug)

Musashi RBP expression during spermatogenesis. dMsi paralogs dMsi and Rbp6 are differentially expressed in the fly testis: dMsi is nuclear and expressed in early germ cells and spermatocytes while Rbp6 is cytoplasmic and localized to spermatogonial cyst cells. Mammalian Msi1 is expressed in the cytoplasm of early mitotic germ cells before translocating to the nucleus upon transition to meiosis. Mammalian Msi2 is entirely nuclear, expressed throughout meiosis and during spermatid differentiation. The dotted line refers to cytoplasmic localization while the solid line refers to nuclear-specific expression. RBP: RNA binding proteins; Msi1: Musashi-1; Msi2: Musashi-2; dMsi: Drosophila Musashi; Rbp6: RNA-binding protein 6.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492041&req=5

Figure 3: Musashi RBP expression during spermatogenesis. dMsi paralogs dMsi and Rbp6 are differentially expressed in the fly testis: dMsi is nuclear and expressed in early germ cells and spermatocytes while Rbp6 is cytoplasmic and localized to spermatogonial cyst cells. Mammalian Msi1 is expressed in the cytoplasm of early mitotic germ cells before translocating to the nucleus upon transition to meiosis. Mammalian Msi2 is entirely nuclear, expressed throughout meiosis and during spermatid differentiation. The dotted line refers to cytoplasmic localization while the solid line refers to nuclear-specific expression. RBP: RNA binding proteins; Msi1: Musashi-1; Msi2: Musashi-2; dMsi: Drosophila Musashi; Rbp6: RNA-binding protein 6.
Mentions: Recent work has by our group detailed the distinctive expression of mammalian Msi1 and Msi2 and explored the outcomes of aberrant expression of both RBPs during the process of male gamete development.100 The unique spatial and temporal expression patterns of the Musashi proteins throughout spermatogenesis indicate individual roles of both RBPs throughout during gamete development in the mammalian testis (Figure 3). Specifically, Msi1 predominately localizes to the cytoplasmic compartments of mitotic gonocytes and spermatogonia, while Msi2 shows nuclear expression in meiotic spermatocytes and differentiating spermatids. The two novel transgenic mouse models utilized, with germ cell-specific overexpression of full-length isoforms of Msi1 or Msi2, demonstrated that aberrant expression of either gene was deleterious to normal spermatogenesis and detrimental to cell health. In addition to this, preliminary studies performed on human testicular seminoma tumors have provided further insights into the relevance of Msi1 and Msi2 over-expression as diagnostic markers to human stem cell cancers.100

Bottom Line: The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted.We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis.This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.

View Article: PubMed Central - PubMed

Affiliation: School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia.

ABSTRACT
Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactive transcription despite heavy translational requirements for continued growth and differentiation. Hence, spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation of gene expression, facilitated by RNA binding proteins (RBPs), which remain abundantly expressed throughout this process. One such group of proteins is the Musashi family, previously identified as critical regulators of testis germ cell development and meiosis in Drosophila, and also shown to be vital to sperm development and reproductive potential in the mouse. This review describes the role and function of RBPs within the scope of male germ cell development, focusing on our recent knowledge of the Musashi proteins in spermatogenesis. The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted. We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis. This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.

No MeSH data available.


Related in: MedlinePlus