DAZL is a master translational regulator of murine spermatogenesis  

作　　者：Haixin Li Zhuqing Liang Jian Yang Dan Wang Hanben Wang Mengyi Zhu Baobao Geng Eugene Yujun Xu 

机构地区：[1]State Key Laboratory of Reproductive Medicine, Nanjing Medical University

出　　处：《National Science Review》2019年第3期455-468,共14页国家科学评论（英文版）

基　　金：supported by the National Basic Research Program of China(2015CB943002 and 2013CB945201);the National Natural Science Foundation of China(31771652,81270737and 81401256);the Natural Science Foundation of Jiangsu Province(BK2012838)

摘　　要：Expression of DAZ-like(DAZL)is a hallmark of vertebrate germ cells,and is essential for embryonic germ cell development and differentiation,yet the gametogenic function of DAZL has not been fully characterized and most of its in vivo direct targets remain unknown.We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility,but caused complete male sterility with gradual loss of spermatogonial stem cells,meiotic arrest and spermatid arrest.Using the genome-wide high-throughput sequencing of RNAs isolated by cross-linking immunoprecipitation and mass spectrometry approach,we found that DAZL bound to a large number of testicular mRNA transcripts(at least 3008)at the 3′-untranslated region and interacted with translation proteins including poly(A)binding protein.In the absence of DAZL,polysome-associated target transcripts,but not their total transcripts,were significantly decreased,resulting in a drastic reduction of an array of spermatogenic proteins and thus developmental arrest.Thus,DAZL is a master translational regulator essential for spermatogenesis.Expression of DAZ-like(DAZL) is a hallmark of vertebrate germ cells, and is essential for embryonic germ cell development and differentiation, yet the gametogenic function of DAZL has not been fully characterized and most of its in vivo direct targets remain unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells, meiotic arrest and spermatid arrest. Using the genome-wide high-throughput sequencing of RNAs isolated by cross-linking immunoprecipitation and mass spectrometry approach, we found that DAZL bound to a large number of testicular m RNA transcripts(at least 3008) at the 3-untranslated region and interacted with translation proteins including poly(A) binding protein. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts, were significantly decreased, resulting in a drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.

关 键 词：RNA binding proteins CLIPS INFERTILITY TRANSLATIONAL regulation DAZ 

分 类 号：N[自然科学总论]