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Dazl regulates germ cell survival through a network of polyA-proximal mRNA interactions
Open accessPreprint — published as 10.1016/j.celrep.2018.10.012
Abstract
Summary: 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.
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Metadata
- Authors
- Zagore, L. L., Sweet, T. J., Hannigan, M. M., Weyn-Vanhentenryck, S. M., Jobava, R., Hatzoglou, M., Zhang, C., & Licatalosi, D. D.
- Affiliations
- Case Western Reserve University (US)
- Columbia University (US)
- Corresponding author
- Licatalosi, Donny D.
- ORCID
- Venue
- Cell Reports
- Publisher
- openRxiv
- Published
- 2018-02-28
- Volume
- 25
- Issue
- 5
- Pages
- 1225-1240.e6
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6878787
- OpenAlex
- W2952593853
- Cited by
- 83
- References
- 1
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 4 · 2023: 6 · 2022: 15 · 2021: 19 · 2020: 18 · 2019: 4 · 2018: 1
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- Funders
- Case Western Reserve University
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM008056, R01GM107331)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Keywords
- DAZL, germ cell survival, RNA-binding proteins, post-transcriptional regulation, male germ cells, germ cell proliferation, gametogenesis
- MeSH terms
- Aging, Animals, Base Sequence, Binding Sites, Cell Cycle, Cell Survival, Female, Gene Expression Regulation, Germ Cells, Male, Mice, Inbred C57BL, Poly A, Protein Binding, RNA, Messenger, Testis, Transcription, Genetic, RNA-Binding Proteins, 5' Untranslated Regions, 3' Untranslated Regions, Gene Regulatory Networks, Transcriptome
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