DAZL is a master translational regulator of murine spermatogenesis

Author:

Li Haixin1,Liang Zhuqing1,Yang Jian1,Wang Dan1,Wang Hanben1,Zhu Mengyi1,Geng Baobao1,Xu Eugene Yujun1

Affiliation:

1. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China

Abstract

Abstract 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.

Funder

National Basic Research Program of China

National Natural Science Foundation of China

Natural Science Foundation of Jiangsu Province

Publisher

Oxford University Press (OUP)

Subject

Multidisciplinary

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