Developmental expression of musashi-1 and musashi-2 rna-binding proteins during spermatogenesis

Analysis of the deleterious effects of dysregulated expression

Jessie M. Sutherland, Barbara A. Fraser, Alexander P. Sobinoff, Victoria J. Pye, Tara Lynne Davidson, Nicole A. Siddall, Peter Koopman, Gary R. Hime, Eileen A. McLaughlin

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Spermatogenesis is a complex developmental process whereby diploid spermatogenic stem cells become haploid and undergo a series of morphological changes to produce physically mature spermatozoa. Crucial to this process are a number of RNA-binding proteins, responsible for the posttranscriptional control of essential mRNAs and particularly pertinent to the two periods of inactive transcription that occur in spermatogenesis. One such group of RNA-binding proteins is the Musashi family, specifically Musashi-1 (MSI1) and Musashi-2 (MSI2), which act as key translational regulators in various stem cell populations and have been linked with the induction of tumorigenesis. In the present study, we examined the differential expression of mammalian MSI1 and MSI2 during germ cell development in the mouse testis. MSI1 was found to be predominately localized in mitotic gonocytes and spermatogonia, whereas MSI2 was detected in meiotic spermatocytes and differentiating spermatids. Extensive examination of the function of Musashi in spermatogenesis was achieved through the use of two transgenic mouse models with germ cell-specific overexpression of fulllength isoforms of Msi1 or Msi2. These models demonstrated that aberrant expression of either Msi1 or Msi2 has deleterious effects on normal spermatogenesis, with Msi2 overexpression resulting in male sterility. Studies undertaken on human testicular seminoma tumors provide further insights into the relevance of MSI1 and MSI2 overexpression as diagnostic markers to human stem cell cancers. Overall this study provides further evidence for the unique functions that RNA-binding protein isoforms occupy within spermatogenesis, and introduces the potential manipulation of the Musashi family proteins to elucidate the mechanisms of posttranscriptional gene expression during germ cell development.

Original languageEnglish
Article number92
Pages (from-to)1-12
Number of pages12
JournalBiology of Reproduction
Volume90
Issue number5
DOIs
Publication statusPublished - 2014
Externally publishedYes

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RNA-Binding Proteins
Spermatogenesis
Germ Cells
Protein Isoforms
Stem Cells
Seminoma
Spermatogonia
Spermatocytes
Spermatids
Neoplastic Stem Cells
Haploidy
Male Infertility
Testicular Neoplasms
Diploidy
Transgenic Mice
Spermatozoa
Testis
Carcinogenesis
Gene Expression
Messenger RNA

Cite this

Sutherland, Jessie M. ; Fraser, Barbara A. ; Sobinoff, Alexander P. ; Pye, Victoria J. ; Davidson, Tara Lynne ; Siddall, Nicole A. ; Koopman, Peter ; Hime, Gary R. ; McLaughlin, Eileen A. / Developmental expression of musashi-1 and musashi-2 rna-binding proteins during spermatogenesis : Analysis of the deleterious effects of dysregulated expression. In: Biology of Reproduction. 2014 ; Vol. 90, No. 5. pp. 1-12.
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Sutherland, JM, Fraser, BA, Sobinoff, AP, Pye, VJ, Davidson, TL, Siddall, NA, Koopman, P, Hime, GR & McLaughlin, EA 2014, 'Developmental expression of musashi-1 and musashi-2 rna-binding proteins during spermatogenesis: Analysis of the deleterious effects of dysregulated expression', Biology of Reproduction, vol. 90, no. 5, 92, pp. 1-12. https://doi.org/10.1095/biolreprod.113.115261

Developmental expression of musashi-1 and musashi-2 rna-binding proteins during spermatogenesis : Analysis of the deleterious effects of dysregulated expression. / Sutherland, Jessie M.; Fraser, Barbara A.; Sobinoff, Alexander P.; Pye, Victoria J.; Davidson, Tara Lynne; Siddall, Nicole A.; Koopman, Peter; Hime, Gary R.; McLaughlin, Eileen A.

In: Biology of Reproduction, Vol. 90, No. 5, 92, 2014, p. 1-12.

Research output: Contribution to journalArticle

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T1 - Developmental expression of musashi-1 and musashi-2 rna-binding proteins during spermatogenesis

T2 - Analysis of the deleterious effects of dysregulated expression

AU - Sutherland, Jessie M.

AU - Fraser, Barbara A.

AU - Sobinoff, Alexander P.

AU - Pye, Victoria J.

AU - Davidson, Tara Lynne

AU - Siddall, Nicole A.

AU - Koopman, Peter

AU - Hime, Gary R.

AU - McLaughlin, Eileen A.

PY - 2014

Y1 - 2014

N2 - Spermatogenesis is a complex developmental process whereby diploid spermatogenic stem cells become haploid and undergo a series of morphological changes to produce physically mature spermatozoa. Crucial to this process are a number of RNA-binding proteins, responsible for the posttranscriptional control of essential mRNAs and particularly pertinent to the two periods of inactive transcription that occur in spermatogenesis. One such group of RNA-binding proteins is the Musashi family, specifically Musashi-1 (MSI1) and Musashi-2 (MSI2), which act as key translational regulators in various stem cell populations and have been linked with the induction of tumorigenesis. In the present study, we examined the differential expression of mammalian MSI1 and MSI2 during germ cell development in the mouse testis. MSI1 was found to be predominately localized in mitotic gonocytes and spermatogonia, whereas MSI2 was detected in meiotic spermatocytes and differentiating spermatids. Extensive examination of the function of Musashi in spermatogenesis was achieved through the use of two transgenic mouse models with germ cell-specific overexpression of fulllength isoforms of Msi1 or Msi2. These models demonstrated that aberrant expression of either Msi1 or Msi2 has deleterious effects on normal spermatogenesis, with Msi2 overexpression resulting in male sterility. Studies undertaken on human testicular seminoma tumors provide further insights into the relevance of MSI1 and MSI2 overexpression as diagnostic markers to human stem cell cancers. Overall this study provides further evidence for the unique functions that RNA-binding protein isoforms occupy within spermatogenesis, and introduces the potential manipulation of the Musashi family proteins to elucidate the mechanisms of posttranscriptional gene expression during germ cell development.

AB - Spermatogenesis is a complex developmental process whereby diploid spermatogenic stem cells become haploid and undergo a series of morphological changes to produce physically mature spermatozoa. Crucial to this process are a number of RNA-binding proteins, responsible for the posttranscriptional control of essential mRNAs and particularly pertinent to the two periods of inactive transcription that occur in spermatogenesis. One such group of RNA-binding proteins is the Musashi family, specifically Musashi-1 (MSI1) and Musashi-2 (MSI2), which act as key translational regulators in various stem cell populations and have been linked with the induction of tumorigenesis. In the present study, we examined the differential expression of mammalian MSI1 and MSI2 during germ cell development in the mouse testis. MSI1 was found to be predominately localized in mitotic gonocytes and spermatogonia, whereas MSI2 was detected in meiotic spermatocytes and differentiating spermatids. Extensive examination of the function of Musashi in spermatogenesis was achieved through the use of two transgenic mouse models with germ cell-specific overexpression of fulllength isoforms of Msi1 or Msi2. These models demonstrated that aberrant expression of either Msi1 or Msi2 has deleterious effects on normal spermatogenesis, with Msi2 overexpression resulting in male sterility. Studies undertaken on human testicular seminoma tumors provide further insights into the relevance of MSI1 and MSI2 overexpression as diagnostic markers to human stem cell cancers. Overall this study provides further evidence for the unique functions that RNA-binding protein isoforms occupy within spermatogenesis, and introduces the potential manipulation of the Musashi family proteins to elucidate the mechanisms of posttranscriptional gene expression during germ cell development.

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KW - Germ cell

KW - Meiosis

KW - Musashi

KW - RNA-binding

KW - Spermatogenesis

KW - Stem cell

KW - Testis

KW - Immunohistochemistry

KW - Meiosis/genetics

KW - Spermatocytes/physiology

KW - Humans

KW - Male

KW - RNA-Binding Proteins/genetics

KW - Spermatogonia/physiology

KW - Gene Expression Regulation, Developmental

KW - Statistics, Nonparametric

KW - Spermatogenesis/physiology

KW - Testis/cytology

KW - Mice, Transgenic

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Blotting, Western

KW - RNA/chemistry

KW - Animals

KW - Protein Isoforms

KW - Mice

KW - Microscopy, Fluorescence

KW - meiosis

KW - testis

KW - stem cell

KW - spermatogenesis

KW - germ cell

KW - cancer

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JO - Biology of Reproduction

JF - Biology of Reproduction

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