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.
| Original language | English |
|---|---|
| Pages (from-to) | 3262-3273 |
| Number of pages | 12 |
| Journal | Journal of Cellular Physiology |
| Volume | 233 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 Apr 2018 |
| Externally published | Yes |
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RNA binding protein Musashi-2 regulates PIWIL1 and TBX1 in mouse spermatogenesis. / Sutherland, Jessie M.; Sobinoff, Alexander P.; Fraser, Barbara A.; Redgrove, Kate A.; Siddall, Nicole A.; Koopman, Peter; Hime, Gary R.; McLaughlin, Eileen A.
In: Journal of Cellular Physiology, Vol. 233, No. 4, 01.04.2018, p. 3262-3273.Research output: Contribution to journal › Article
TY - JOUR
T1 - RNA binding protein Musashi-2 regulates PIWIL1 and TBX1 in mouse spermatogenesis
AU - Sutherland, Jessie M.
AU - Sobinoff, Alexander P.
AU - Fraser, Barbara A.
AU - Redgrove, Kate A.
AU - Siddall, Nicole A.
AU - Koopman, Peter
AU - Hime, Gary R.
AU - McLaughlin, Eileen A.
N1 - © 2017 Wiley Periodicals, Inc.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
KW - gametogenesis
KW - MSI2
KW - RBP
KW - spermatid
KW - testes
UR - http://www.scopus.com/inward/record.url?scp=85038954303&partnerID=8YFLogxK
U2 - 10.1002/jcp.26168
DO - 10.1002/jcp.26168
M3 - Article
VL - 233
SP - 3262
EP - 3273
JO - Journal of cellular and comparative physiology
JF - Journal of cellular and comparative physiology
SN - 0021-9541
IS - 4
ER -