Poster abstracts
Poster number 25 submitted by Leah Zagore
Dazl regulates germ cell survival through a network of polyA-proximal mRNA interactions
Leah L. Zagore (Center for RNA Science and Therapeutics, Case Western Reserve University), Thomas J. Sweet (Center for RNA Science and Therapeutics, Case Western Reserve University), Molly M. Hannigan (Center for RNA Science and Therapeutics, Case Western Reserve University), Sebastien M. Weyn-Vanhentenryck, Chaolin Zhang (Center for Motor Neuron Biology and Disease, Columbia University,), Donny D. Licatalosi (Center for RNA Science and Therapeutics, Case Western Reserve University)
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 critical for germ cell proliferation and survival. Additionally, we provide evidence that polyA sequences have key roles in specifying Dazl-RNA interactions across the transcriptome. Altogether, 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: post-transcriptional gene regulation, RNA binding proteins, RNA networks