Journal
ELIFE
Volume 9, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.56523
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Funding
- Howard Hughes Medical Institute Page laboratory
- Lalor Foundation
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [F32HD093391]
- National Natural Science Foundation of China [81471507]
- National Key Research and Development Program of China [2017YFC1001600]
- Hope Funds for Cancer Research [HFCR-15-06-06]
- National Health and Medical Research Council [GNT1053776]
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Fertility across metazoa requires the germline-specific DAZ family of RNA-binding proteins. Here we examine whether DAZL directly regulates progenitor spermatogonia using a conditional genetic mouse model and in vivo biochemical approaches combined with chemical synchronization of spermatogenesis. We find that the absence of Dazl impairs both expansion and differentiation of the spermatogonial progenitor population. In undifferentiated spermatogonia, DAZL binds the 3' UTRs of similar to 2,500 protein-coding genes. Some targets are known regulators of spermatogonial proliferation and differentiation while others are broadly expressed, dosage-sensitive factors that control transcription and RNA metabolism. DAZL binds 3' UTR sites conserved across vertebrates at a UGUU(U/A) motif. By assessing ribosome occupancy in undifferentiated spermatogonia, we find that DAZL increases translation of its targets. In total, DAZL orchestrates a broad translational program that amplifies protein levels of key spermatogonial and gene regulatory factors to promote the expansion and differentiation of progenitor spermatogonia.
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