2. Academic Validation
  3. DAZL regulates proliferation of human primordial germ cells by direct binding to precursor miRNAs and enhances DICER processing activity

DAZL regulates proliferation of human primordial germ cells by direct binding to precursor miRNAs and enhances DICER processing activity

  • Nucleic Acids Res. 2022 Oct 28;50(19):11255-11272. doi: 10.1093/nar/gkac856.
An Yan 1,  Jie Xiong 1 2,  Jiadong Zhu 1,  Xiangyu Li 3 4,  Shuting Xu 1 2,  Xiaoyu Feng 1,  Xin Ke 5,  Zhenyi Wang 4,  Yang Chen 4 6,  Hong-Wei Wang 5,  Michael Q Zhang 4 6 7,  Kehkooi Kee 1 2
Affiliations

Affiliations

  • 1 Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
  • 2 Tsinghua University--Peking University Joint Center for Life Sciences, Tsinghua University, Beijing 100084, China.
  • 3 School of Software Engineering, Beijing Jiaotong University, Beijing 100044, China.
  • 4 MOE Key Laboratory of Bioinformatics; Bioinformatics Division and Center for Synthetic & Systems Biology, BNRist; Department of Automation, Tsinghua University, Beijing 100084, China.
  • 5 Ministry of Education Key Laboratory of Protein Sciences, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084,China.
  • 6 School of Medicine, Tsinghua University, Beijing 100084, China.
  • 7 Department of Biological Sciences, Center for Systems Biology, The University of Texas at Dallas, 800 West Campbell Road, RL11, Richardson, TX 75080-3021, USA.
PMID: 36273819 DOI: 10.1093/nar/gkac856
Abstract

Understanding the molecular and cellular mechanisms of human primordial germ cells (hPGCs) is essential in studying infertility and germ cell tumorigenesis. Many RNA-binding proteins (RBPs) and non-coding RNAs are specifically expressed and functional during hPGC developments. However, the roles and regulatory mechanisms of these RBPs and non-coding RNAs, such as MicroRNAs (miRNAs), in hPGCs remain elusive. In this study, we reported a new regulatory function of DAZL, a germ cell-specific RBP, in miRNA biogenesis and cell proliferation. First, DAZL co-localized with miRNA let-7a in human PGCs and up-regulated the levels of >100 mature miRNAs, including eight out of nine let-7 family, miR21, miR22, miR125, miR10 and miR199. Purified DAZL directly bound to the loops of precursor miRNAs with sequence specificity of GUU. The binding of DAZL to the precursor miRNA increased the maturation of miRNA by enhancing the cleavage activity of DICER. Furthermore, cell proliferation assay and cell cycle analysis confirmed that DAZL inhibited the proliferation of in vitro PGCs by promoting the maturation of these miRNAs. Evidently, the mature miRNAs up-regulated by DAZL silenced cell proliferation regulators including TRIM71. Moreover, DAZL inhibited germline tumor cell proliferation and teratoma formation. These results demonstrate that DAZL regulates hPGC proliferation by enhancing miRNA processing.

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