RNA binding protein Musashi‐1 directly targetsMsi2andErhduring early testis germ cell development and interacts with IPO5 upon translocation to the nucleus
RNA binding protein Musashi‐1 directly targetsMsi2andErhduring early testis germ cell development and interacts with IPO5 upon translocation to the nucleus
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.
- University of Melbourne Australia
- University of Queensland Australia
- University of Queensland Australia
- University of Newcastle Australia Australia
- University of Queensland Australia
Male, MSI1, germ cells, 1303 Biochemistry, mice, 571, Molecular Sequence Data, Active Transport, Cell Nucleus, posttranscriptional regulation, Cell Cycle Proteins, Mice, Transgenic, Nerve Tissue Proteins, Models, Biological, Mice, 1311 Genetics, RBP, Spermatocytes, XXXXXX - Unknown, Testis, 1312 Molecular Biology, meiosis, Animals, Amino Acid Sequence, Spermatogenesis, Gene Expression Regulation, Developmental, RNA-Binding Proteins, beta Karyopherins, spermatogenesis, Spermatogonia, 1305 Biotechnology, Drosophila, Posttranscriptional regulation, Transcription Factors
Male, MSI1, germ cells, 1303 Biochemistry, mice, 571, Molecular Sequence Data, Active Transport, Cell Nucleus, posttranscriptional regulation, Cell Cycle Proteins, Mice, Transgenic, Nerve Tissue Proteins, Models, Biological, Mice, 1311 Genetics, RBP, Spermatocytes, XXXXXX - Unknown, Testis, 1312 Molecular Biology, meiosis, Animals, Amino Acid Sequence, Spermatogenesis, Gene Expression Regulation, Developmental, RNA-Binding Proteins, beta Karyopherins, spermatogenesis, Spermatogonia, 1305 Biotechnology, Drosophila, Posttranscriptional regulation, Transcription Factors
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