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RNA binding protein Musashi-2 regulates PIWIL1 and TBX1 in mouse spermatogenesis

Journal Article


Abstract


  • RNA-binding proteins (RBP) are important facilitators of post-transcriptional gene regulation. We have previously established that nuclear overexpression of the RBP Musashi-2 (MSI2) during male germ cell maturation is detrimental to sperm cell development and fertility. Herein we determine the genes and pathways impacted by the upregulation of Msi2. Microarray analysis and qPCR confirmed differential gene expression in factors fundamental to the cell cycle, cellular proliferation, and cell death. Similarly, comparative protein expression analysis via iTRAQ, immunoblot, and immunolocalization, identified differential expression and localization of important regulators of transcription, translation, RNA processing, and spermatogenesis. Specifically, the testis-expressed transcription factor, Tbx1, and the piRNA regulator of gamete development, Piwil1, were both found to be targeted for translational repression by MSI2. This study provides key evidence to support a fundamental role for MSI2 in post-transcriptional regulation during male gamete development.

Publication Date


  • 2018

Citation


  • Sutherland, J. M., Sobinoff, A. P., Fraser, B. A., Redgrove, K. A., Siddall, N. A., Koopman, P., . . . McLaughlin, E. A. (2018). RNA binding protein Musashi-2 regulates PIWIL1 and TBX1 in mouse spermatogenesis. Journal of Cellular Physiology, 233(4), 3262-3273. doi:10.1002/jcp.26168

Scopus Eid


  • 2-s2.0-85038954303

Start Page


  • 3262

End Page


  • 3273

Volume


  • 233

Issue


  • 4

Place Of Publication


Abstract


  • RNA-binding proteins (RBP) are important facilitators of post-transcriptional gene regulation. We have previously established that nuclear overexpression of the RBP Musashi-2 (MSI2) during male germ cell maturation is detrimental to sperm cell development and fertility. Herein we determine the genes and pathways impacted by the upregulation of Msi2. Microarray analysis and qPCR confirmed differential gene expression in factors fundamental to the cell cycle, cellular proliferation, and cell death. Similarly, comparative protein expression analysis via iTRAQ, immunoblot, and immunolocalization, identified differential expression and localization of important regulators of transcription, translation, RNA processing, and spermatogenesis. Specifically, the testis-expressed transcription factor, Tbx1, and the piRNA regulator of gamete development, Piwil1, were both found to be targeted for translational repression by MSI2. This study provides key evidence to support a fundamental role for MSI2 in post-transcriptional regulation during male gamete development.

Publication Date


  • 2018

Citation


  • Sutherland, J. M., Sobinoff, A. P., Fraser, B. A., Redgrove, K. A., Siddall, N. A., Koopman, P., . . . McLaughlin, E. A. (2018). RNA binding protein Musashi-2 regulates PIWIL1 and TBX1 in mouse spermatogenesis. Journal of Cellular Physiology, 233(4), 3262-3273. doi:10.1002/jcp.26168

Scopus Eid


  • 2-s2.0-85038954303

Start Page


  • 3262

End Page


  • 3273

Volume


  • 233

Issue


  • 4

Place Of Publication