Ribosome biogenesis protein Urb1 acts downstream of mTOR complex 1 to modulate digestive organ development in zebrafish
Autor: | Jia He, Jinzi Chen, Lingfei Luo, Xiangyong Wei, Yun Yang, Junren Zhang, Jianbo He |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Ribosome biogenesis mTORC1 Biology Mechanistic Target of Rapamycin Complex 1 03 medical and health sciences Mice Polysome Genetics Protein biosynthesis Animals Humans Amino Acid Sequence Molecular Biology Zebrafish PI3K/AKT/mTOR pathway Cell Proliferation Gene knockdown Base Sequence Cell growth Endoderm Nuclear Proteins Cell Differentiation Zebrafish Proteins biology.organism_classification Cell biology Gastrointestinal Tract 030104 developmental biology Mutation Ribosomes Signal Transduction |
Zdroj: | Journal of genetics and genomics = Yi chuan xue bao. 44(12) |
ISSN: | 1673-8527 |
Popis: | 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. |
Databáze: | OpenAIRE |
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