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GEO help: Mouse over screen elements for information. |
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Status |
Public on Nov 29, 2022 |
Title |
DAZL regulates proliferation of human primordial germ cell by direct binding to precursor miRNAs and enhances DICER processing activity |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
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Summary |
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 cellspecific RBP, in miRNA biogenesis and cell proliferation. First, DAZL colocalized with miRNA let-7a in human PGCs and upregulated the levels of over a hundred mature miRNAs, including eight out of nine let-7 family, 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 upregulated 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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Overall design |
Comparative gene expression profiling analysis of RNA-seq data for WT PGCLCs and oeDAZL PGCLCs and expression profiling analysis of miRNA-seq for WT PGCLCs and its derivatives (shDAZL_4,shDAZL_6).
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Contributor(s) |
Xiaoyu F, Shuting X |
Citation(s) |
36273819 |
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Submission date |
Jun 20, 2022 |
Last update date |
Nov 29, 2022 |
Contact name |
XIAOYU FENG |
Organization name |
Tsinghua University
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Street address |
QINGHUAYUAN street,HAIDIAN distribute
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City |
BEIJING |
State/province |
BEIJING |
ZIP/Postal code |
100084 |
Country |
China |
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Platforms (2) |
GPL18460 |
Illumina HiSeq 1500 (Homo sapiens) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (10)
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Relations |
BioProject |
PRJNA851041 |
Supplementary file |
Size |
Download |
File type/resource |
GSE206466_mirna_count.xlsx |
171.0 Kb |
(ftp)(http) |
XLSX |
GSE206466_pgclcs_expr_tpm.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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