DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial progenitors.

ELife
Maria M MikedisDavid C Page

Abstract

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 ~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.

References

Sep 1, 1991·Journal of Reproduction and Fertility·R P VergouwenD G de Rooij
Jan 1, 1984·Anatomy and Embryology·P M KluinD G de Rooij
Jan 1, 1996·Hormone Research·Y NakahoriK Kobayashi
Aug 1, 1997·Human Reproduction·S K GirardiP N Schlegel
May 20, 1998·Biochemical and Biophysical Research Communications·J Seligman, D C Page
Aug 24, 1999·Biology of Reproduction·D G de RooijY Nishimune
Jun 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·E Y XuR A Pera
Aug 22, 2001·Biology of Reproduction·B H Schrans-StassenD G de Rooij
Jun 7, 2002·Mechanisms of Development·Piroska E SzabóJeffrey R Mann
Sep 26, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Shingo MaegawaKunio Inoue
Nov 13, 2003·Reproduction : the Official Journal of the Society for the Study of Fertility·P T K SaundersH J Cooke
Jul 19, 2005·Genome Research·Adam SiepelDavid Haussler
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 29, 2005·Developmental Biology·Yanfeng Lin, David C Page
Aug 19, 2007·Cancer Research·Charles D JohnsonFrank J Slack
Feb 23, 2008·Science·Srinivas R ViswanathanRichard I Gregory
Oct 18, 2008·Nature Reviews. Genetics·William F MarzluffRobert J Duronio
Oct 29, 2008·Genome Research·Robin C FriedmanDavid P Bartel
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Elisenda SanzPaul S Amieux
Oct 15, 2009·The Journal of Pathology·Reiner A Veitia, James A Birchler
Oct 28, 2009·Genome Research·Katherine S PollardAdam Siepel
Apr 2, 2010·BMC Bioinformatics·Robert C McLeay, Timothy L Bailey
Jul 6, 2010·Nature Structural & Molecular Biology·Julian KönigJernej Ule
Oct 27, 2010·PLoS Genetics·Ni HuangMatthew E Hurles
Apr 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Mark E GillDavid C Page
Aug 26, 2011·The Journal of Clinical Investigation·Meredith J GoertzDiego H Castrillon

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Citations

Dec 1, 2020·Molecular Reproduction and Development·Zachariah L McLeanBjörn Oback
Apr 4, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Anna Laura VoigtIna Dobrinski
Apr 30, 2021·Development·Peter K Nicholls, David C Page
May 5, 2021·Frontiers in Cell and Developmental Biology·Kai O SkaftnesmoAnna Wargelius
Nov 9, 2021·Cellular and Molecular Life Sciences : CMLS·Marcos MorganMarine Baptissart

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Datasets Mentioned

BETA
GSE102783
GSM2746356
GSM2746357
DRA002477
DRR022939
DRR022945
GSE107124
GSE125483
GSE108183
GSE145177

Methods Mentioned

BETA
iCLIP
RNA-seq
biopsy
CLIP
immunoprecipitation
IP-seq
confocal microscopy
Fluorescence
FACS
PCR

Software Mentioned

MetaPlotR
Cutadapt
ASPeak
GSEAPreranked
Ensembl
AmiGO
coRdon
fastx
kallisto
HOMER

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