PUBLICATION

Loss of the RNA-binding protein Rbm15 disrupts liver maturation in zebrafish

Authors
Hu, L., Li, H., Chi, Z., He, J.
ID
ZDB-PUB-200611-4
Date
2020
Source
The Journal of biological chemistry   295(33): 11466-11472 (Journal)
Registered Authors
He, Jianbo
Keywords
RNA binding motif protein 15 (Rbm15), RNA binding protein, gene regulation, hepatocyte nuclear factor 4 (HNF-4), liver maturation, liver organogenesis, mTORC1, post-transcriptional regulation, zebrafish
MeSH Terms
  • Liver/cytology
  • Liver/embryology*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Apoptosis
  • Hepatocytes/cytology
  • Hepatocytes/metabolism
  • Cell Proliferation
  • Gene Deletion*
  • Cell Differentiation
  • CRISPR-Cas Systems
  • Gene Expression Regulation, Developmental*
  • Animals
(all 13)
PubMed
32518161 Full text @ J. Biol. Chem.
Abstract
Liver organogenesis begins with hepatic precursors in the foregut endoderm, followed by hepatoblast specification, differentiation, outgrowth, and maturation for the formation of functional hepatocytes. Although several signaling pathways and critical factors that regulate liver specification, differentiation, and proliferation have been identified, little is known about how liver maturation is regulated. Here, we used a screen for mutations affecting liver development in zebrafish and identified a cq96 mutant that exhibits a specific defect in liver maturation. Results from positional cloning revealed that cq96 encodes an RNA-binding protein, Rbm15, which is an evolutionarily conserved Spen family protein and known to play a crucial role in RNA m6A modification, nuclear export, and alternative splicing. However, a function of Rbm15 in embryonic liver development has not been reported. We found that Rbm15 is specifically expressed in the liver after its differentiation. CRISPR/Cas9-mediated loss of rbm15 repressed hepatic maturation, but did not affect hepatoblast specification, differentiation, and hepatocyte proliferation and apoptosis. Additional experiments disclosed that the mTOR complex 1 (mTORC1) pathway is highly activated in rbm15-deficient hepatocytes. Moreover, rapamycin treatment partially restored normal hepatic gene expression as well as the nuclear location of the transcription factor Hnf4a. Taken together, these results reveal an unexpected role of Rbm15 in liver maturation.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cq1TgTransgenic Insertion
    cq96
      Small Deletion
      cq97TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        rbm15CRISPR1-rbm15CRISPR
        1 - 1 of 1
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        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        Ab1-eif4ebp1monoclonalIgGRabbit
        ab1-hnf4apolyclonalIgGGoat
        Ab-2F11monoclonalIgG1Mouse
        Ab3-prox1polyclonalRabbit
        Ab10-pcnapolyclonal
          Rabbit
          1 - 5 of 5
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          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          Dendra2EFGDendra2
          NTREFGNTR
          1 - 2 of 2
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          Mapping
          No data available