RNA binding protein Musashi-1 directly targets Msi2 and Erh during early testis germ cell development and interacts with IPO5 upon translocation to the nucleus

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the process of gamete development, male germ cells experience extended periods of inactive transcription despite requirements for continued growth and differentiation. Spermatogenesis therefore provides an ideal model to study the effects of posttranscriptional control on gene regulation. During spermatogenesis posttranscriptional regulation is orchestrated by abundantly expressed RNA-binding proteins. One such group of RNA-binding proteins is the Musashi family, previously identified as a critical regulator of testis germ cell development and meiosis in Drosophila and also shown to be vital to sperm development and reproductive potential in the mouse. We focus in depth on the role and function of the vertebrate Musashi ortholog Musashi-1 (MSI1). Through detailed expression studies and utilizing our novel transgenic Msi1 testis-specific overexpression model, we have identified 2 unique RNA-binding targets of MSI1 in spermatogonia,Msi2 and Erh, and have demonstrated a role for MSI1 in translational regulation. We have also provided evidence to suggest that nuclear import protein, IPO5, facilitates the nuclear translocation of MSI1 to the transcriptionally silenced XY chromatin domain in meiotic pachytene spermatocytes, resulting in the release of MSI1 RNA-binding targets. This firmly establishes MSI1 as a master regulator of posttranscriptional control during early spermatogenesis and highlights the significance of the subcellular localization of RNA binding proteins in relation to their function.

Original languageEnglish
Pages (from-to)2759-2768
Number of pages10
JournalFASEB Journal
Volume29
Issue number7
DOIs
Publication statusPublished - 1 Jul 2015
Externally publishedYes

Fingerprint

RNA-Binding Proteins
Germ Cells
Testis
Spermatogenesis
Cells
Gene expression
RNA
Transcription
Spermatogonia
Chromatin
Spermatocytes
Cell Nucleus Active Transport
Meiosis
Nuclear Proteins
Genes
Drosophila
Vertebrates
Spermatozoa
Growth

Cite this

Sutherland, J. M., Sobinoff, A. P., Fraser, B. A., Redgrove, K. A., Davidson, T. L., Siddall, N. A., ... McLaughlin, E. A. (2015). RNA binding protein Musashi-1 directly targets Msi2 and Erh during early testis germ cell development and interacts with IPO5 upon translocation to the nucleus. FASEB Journal, 29(7), 2759-2768. https://doi.org/10.1096/fj.14-265868
Sutherland, Jessie M. ; Sobinoff, Alexander P. ; Fraser, Barbara A. ; Redgrove, Kate A. ; Davidson, Tara Lynne ; Siddall, Nicole A. ; Koopman, Peter ; Hime, Gary R. ; McLaughlin, Eileen A. / RNA binding protein Musashi-1 directly targets Msi2 and Erh during early testis germ cell development and interacts with IPO5 upon translocation to the nucleus. In: FASEB Journal. 2015 ; Vol. 29, No. 7. pp. 2759-2768.
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Sutherland, JM, Sobinoff, AP, Fraser, BA, Redgrove, KA, Davidson, TL, Siddall, NA, Koopman, P, Hime, GR & McLaughlin, EA 2015, 'RNA binding protein Musashi-1 directly targets Msi2 and Erh during early testis germ cell development and interacts with IPO5 upon translocation to the nucleus', FASEB Journal, vol. 29, no. 7, pp. 2759-2768. https://doi.org/10.1096/fj.14-265868

RNA binding protein Musashi-1 directly targets Msi2 and Erh during early testis germ cell development and interacts with IPO5 upon translocation to the nucleus. / Sutherland, Jessie M.; Sobinoff, Alexander P.; Fraser, Barbara A.; Redgrove, Kate A.; Davidson, Tara Lynne; Siddall, Nicole A.; Koopman, Peter; Hime, Gary R.; McLaughlin, Eileen A.

In: FASEB Journal, Vol. 29, No. 7, 01.07.2015, p. 2759-2768.

Research output: Contribution to journalArticle

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T1 - RNA binding protein Musashi-1 directly targets Msi2 and Erh during early testis germ cell development and interacts with IPO5 upon translocation to the nucleus

AU - Sutherland, Jessie M.

AU - Sobinoff, Alexander P.

AU - Fraser, Barbara A.

AU - Redgrove, Kate A.

AU - Davidson, Tara Lynne

AU - Siddall, Nicole A.

AU - Koopman, Peter

AU - Hime, Gary R.

AU - McLaughlin, Eileen A.

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AB - Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the process of gamete development, male germ cells experience extended periods of inactive transcription despite requirements for continued growth and differentiation. Spermatogenesis therefore provides an ideal model to study the effects of posttranscriptional control on gene regulation. During spermatogenesis posttranscriptional regulation is orchestrated by abundantly expressed RNA-binding proteins. One such group of RNA-binding proteins is the Musashi family, previously identified as a critical regulator of testis germ cell development and meiosis in Drosophila and also shown to be vital to sperm development and reproductive potential in the mouse. We focus in depth on the role and function of the vertebrate Musashi ortholog Musashi-1 (MSI1). Through detailed expression studies and utilizing our novel transgenic Msi1 testis-specific overexpression model, we have identified 2 unique RNA-binding targets of MSI1 in spermatogonia,Msi2 and Erh, and have demonstrated a role for MSI1 in translational regulation. We have also provided evidence to suggest that nuclear import protein, IPO5, facilitates the nuclear translocation of MSI1 to the transcriptionally silenced XY chromatin domain in meiotic pachytene spermatocytes, resulting in the release of MSI1 RNA-binding targets. This firmly establishes MSI1 as a master regulator of posttranscriptional control during early spermatogenesis and highlights the significance of the subcellular localization of RNA binding proteins in relation to their function.

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KW - RBP

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KW - Transcription Factors/genetics

KW - Animals

KW - Gene Expression Regulation, Developmental

KW - Models, Biological

KW - Nerve Tissue Proteins/genetics

KW - Spermatogonia/metabolism

KW - beta Karyopherins/genetics

KW - Cell Cycle Proteins/genetics

KW - Mice

KW - Active Transport, Cell Nucleus

KW - Spermatocytes/metabolism

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DO - 10.1096/fj.14-265868

M3 - Article

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SP - 2759

EP - 2768

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

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