PUBLICATION

Ribosome biogenesis protein Urb1 acts downstream of mTOR complex 1 to modulate digestive organ development in zebrafish

Authors
He, J., Yang, Y., Zhang, J., Chen, J., Wei, X., He, J., Luo, L.
ID
ZDB-PUB-171219-3
Date
2017
Source
Journal of genetics and genomics = Yi chuan xue bao   44(12): 567-576 (Journal)
Registered Authors
He, Jianbo, Luo, Lingfei, Yang, Yun
Keywords
Digestive organ development, Ribosome biogenesis protein, Urb1, Zebrafish, mTORC1
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Differentiation
  • Cell Proliferation
  • Endoderm/cytology
  • Gastrointestinal Tract/cytology
  • Gastrointestinal Tract/embryology*
  • Gastrointestinal Tract/metabolism
  • Humans
  • Mechanistic Target of Rapamycin Complex 1/metabolism*
  • Mice
  • Mutation
  • Nuclear Proteins/chemistry
  • Nuclear Proteins/genetics
  • Nuclear Proteins/metabolism*
  • Ribosomes/metabolism*
  • Signal Transduction
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
29246861 Full text @ J. Genet. Genomics
Abstract
Ribosome biogenesis is essential for the cell growth and division. Disruptions in ribosome biogenesis result in developmental defects and a group of diseases, known as ribosomopathies. Here, we report a mutation in zebrafish urb1, which encodes an essential ribosome biogenesis protein. The urb1cq31 mutant exhibits hypoplastic digestive organs, which is caused by impaired cell proliferation with the differentiation of digestive organ progenitors unaffected. Knockdown of mtor or raptor leads to similar hypoplastic phenotypes and reduced expression of urb1 in the digestive organs. Overexpression of Urb1 results in overgrowth of digestive organs, and can efficiently rescue the hypoplastic liver and pancreas in the mtor and raptor morphants. Reduced syntheses of free ribosomal subunits and impaired assembly of polysomes are observed in the urb1 mutant as well as in the mtor and raptor morphants, which can be rescued by the Urb1 overexpression. These data demonstrate that Urb1 plays an important role in governing ribosome biogenesis and protein synthesis downstream of mammalian/mechanistic target of rapamycin complex 1 (mTORC1), thus regulating the development of digestive organs. Our study indicates the requirement of hyperactive protein synthesis for the digestive organ development.
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Human Disease / Model
Sequence Targeting Reagents
Fish
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