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Cell Rep. 2018 Oct 30;25(5):1225-1240.e6. doi: 10.1016/j.celrep.2018.10.012.

DAZL Regulates Germ Cell Survival through a Network of PolyA-Proximal mRNA Interactions.

Author information

1
Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USA.
2
Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA.
3
Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
4
Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: ddl33@case.edu.

Abstract

The RNA binding protein DAZL is essential for gametogenesis, but its direct in vivo functions, RNA targets, and the molecular basis for germ cell loss in Dazl-null mice are unknown. Here, we mapped transcriptome-wide DAZL-RNA interactions in vivo, revealing DAZL binding to thousands of mRNAs via polyA-proximal 3' UTR interactions. In parallel, fluorescence-activated cell sorting and RNA-seq identified mRNAs sensitive to DAZL deletion in male germ cells. Despite binding a broad set of mRNAs, integrative analyses indicate that DAZL post-transcriptionally controls only a subset of its mRNA targets, namely those corresponding to a network of genes that are critical for germ cell proliferation and survival. In addition, we provide evidence that polyA sequences have key roles in specifying DAZL-RNA interactions across the transcriptome. Our results reveal a mechanism for DAZL-RNA binding and illustrate that DAZL functions as a master regulator of a post-transcriptional mRNA program essential for germ cell survival.

KEYWORDS:

3′ UTR; DAZL; RNA binding protein; RNA networks; germ cell survival; post-transcriptional regulation; spermatogenesis

PMID:
30380414
DOI:
10.1016/j.celrep.2018.10.012
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