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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions / genetics
  • 5' Untranslated Regions / genetics
  • Aging
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Cycle / genetics
  • Cell Survival
  • Female
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Germ Cells / cytology*
  • Germ Cells / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Poly A / metabolism*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Testis / metabolism
  • Transcription, Genetic
  • Transcriptome / genetics


  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • DAZL protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • Poly A