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. and McLaughlin, Eileen 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. The FASEB Journal, 29 7: 2759-2768. doi:10.1096/fj.14-265868


Author 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.
Title 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
Journal name The FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
1530-6860
Publication date 2015-03-17
Year available 2015
Sub-type Article (original research)
DOI 10.1096/fj.14-265868
Open Access Status Not yet assessed
Volume 29
Issue 7
Start page 2759
End page 2768
Total pages 10
Place of publication Bethesda, MD United States
Publisher Federation of American Societies for Experimental Biology
Language eng
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.
Formatted 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.—Sutherland, J. M., Sobinoff, A. P., Fraser, B. A., Redgrove, K. A., Davidson, T.-L., Siddall, N. A., Koopman, P., Hime, G. R. , McLaughlin, E. 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.
Keyword Posttranscriptional regulation
Spermatogenesis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 5 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 27 Jun 2015, 01:23:25 EST by Susan Allen on behalf of Institute for Molecular Bioscience