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Volume 44 Issue 12
Dec.  2017
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Ribosome biogenesis protein Urb1 acts downstream of mTOR complex 1 to modulate digestive organ development in zebrafish

doi: 10.1016/j.jgg.2017.09.013
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  • Corresponding author: E-mail address: lluo@swu.edu.cn (Lingfei Luo)
  • Received Date: 2017-05-27
  • Accepted Date: 2017-09-28
  • Rev Recd Date: 2017-09-27
  • Available Online: 2017-11-29
  • Publish Date: 2017-12-20
  • 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. Theurb1 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.
  • These authors contributed equally to this work.
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  • [1]
    Alcarazpérez, F., Mulero, V., Cayuela, M.L. Application of the dual-luciferase reporter assay to the analysis of promoter activity in Zebrafish embryos BMC Biotechnol., 8 (2008),p. 81
    [2]
    Avruch, J., Long, X., Ortiz-Vega, S. et al. Amino acid regulation of TOR complex 1 Am. J. Physiol. Endocrinol. Metab., 296 (2009),pp. e592-602
    [3]
    Bielczyk-Maczyńska, E., Lam, H.L., Ferreira, L. et al. The ribosome biogenesis protein Nol9 is essential for definitive hematopoiesis and pancreas morphogenesis in zebrafish PLoS Genet., 11 (2015)
    [4]
    Boglev, Y., Badrock, A.P., Trotter, A.J. et al. Autophagy induction is a Tor- and Tp53-independent cell survival response in a zebrafish model of disrupted ribosome biogenesis PLoS Genet., 9 (2013)
    [5]
    Boultwood, J., Yip, B.H., Vuppusetty, C. et al. Activation of the mTOR pathway by the amino acid (L)-leucine in the 5q-syndrome and other ribosomopathies Adv. Biol. Regul., 53 (2013),pp. 8-17
    [6]
    Buszczak, M., Signer, R.A., Morrison, S.J. Cellular differences in protein synthesis regulate tissue homeostasis Cell, 159 (2014),pp. 242-251
    [7]
    Dez, C., Froment, C., Noaillac-Depeyre, J. et al. Npa1p, a component of very early pre-60S ribosomal particles, associates with a subset of small nucleolar RNPs required for peptidyl transferase center modification Mol. Cell. Biol., 24 (2004),pp. 6324-6337
    [8]
    Dibble, C.C., Cantley, L.C. Regulation of mTORC1 by PI3K signaling Trends Cell Biol., 25 (2015),pp. 545-555
    [9]
    Dibble, C.C., Manning, B.D. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output Nat. Cell Biol., 15 (2013),pp. 555-564
    [10]
    Doudna, J.A., Rath, V.L. Structure and function of the eukaryotic ribosome: the next frontier Cell, 109 (2002),pp. 153-156
    [11]
    Ear, J., Hsueh, J., Nguyen, M. et al. J. Genet. Genomics, 43 (2016),pp. 307-318
    [12]
    Field, H.A., Ober, E.A., Roeser, T. et al. Formation of the digestive system in zebrafish. I. Liver morphogenesis Dev. Biol., 253 (2003),pp. 279-290
    [13]
    Freed, E.F., Baserga, S.J. The C-terminus of Utp4, mutated in childhood cirrhosis, is essential for ribosome biogenesis Nucleic Acids Res., 38 (2010),pp. 4798-4806
    [14]
    Gangloff, Y.G., Mueller, M., Dann, S.G. et al. Mol. Cell. Biol., 24 (2004),pp. 9508-9516
    [15]
    García-Gómez, J.J., Fernández-Pevida, A., Lebaron, S. et al. Final pre-40S maturation depends on the functional integrity of the 60S subunit ribosomal protein L3 PLoS Genet., 10 (2014)
    [16]
    Guertin, D.A., Stevens, D.M., Thoreen, C.C. et al. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1 Dev. Cell, 11 (2006),pp. 859-871
    [17]
    He, J., Lu, H., Zou, Q. et al. Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary transdifferentiation in zebrafish Gastroenterology, 146 (2014),pp. 789-800
    [18]
    Iadevaia, V., Wang, X., Yao, Z. et al. Roles of the mammalian target of rapamycin, mTOR, in controlling ribosome biogenesis and protein synthesis Methods Mol. Biol., 821 (2012),pp. 171-185
    [19]
    Iadevaia, V., Liu, R., Proud, C.G. mTORC1 signaling controls multiple steps in ribosome biogenesis Semin. Cell Dev. Biol., 36 (2014),pp. 113-120
    [20]
    Kim, S.G., Buel, G.R., Blenis, J. Nutrient regulation of the mTOR complex 1 signaling pathway Mol. Cells, 35 (2013),pp. 463-473
    [21]
    Lafontaine, D.L., Tollervey, D. The function and synthesis of ribosome Nat. Rev. Mol. Cell Biol., 2 (2001),pp. 514-520
    [22]
    Liu, C., Wu, C., Yang, Q. et al. Macrophages mediate the repair of brain vascular rupture through direct physical adhesion and mechanical traction Immunity, 44 (2016),pp. 1162-1176
    [23]
    Liu, X., Huang, S., Ma, J. et al. NF-kappaB and Snail1a coordinate the cell cycle with gastrulation J. Cell Biol., 184 (2009),pp. 805-815
    [24]
    Lu, H., Ma, J., Yang, Y. et al. EpCAM is an endoderm-specific Wnt derepressor that licenses hepatic development Dev. Cell, 24 (2009),pp. 543-553
    [25]
    Makky, K., Tekiela, J., Mayer, A.N. Target of rapamycin (TOR) signaling controls epithelial morphogenesis in the vertebrate intestine Dev. Biol., 303 (2007),pp. 501-513
    [26]
    Mayer, A.N., Fishman, M.C. Nil per os encodes a conserved RNA recognition motif protein required for morphogenesis and cytodifferentiation of digestive organs in zebrafish Development, 130 (2003),pp. 3917-3928
    [27]
    Murakami, M., Ichisaka, T., Maeda, M. et al. mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells Mol. Cell. Biol., 24 (2004),pp. 6710-6718
    [28]
    Payne, E.M., Virgilio, M., Narla, A. et al. L-Leucine improves the anemia and developmental defects associated with Diamond-Blackfan anemia and del (5q) MDS by activating the mTOR pathway Blood, 120 (2012),pp. 2214-2224
    [29]
    Pópulo, H., Lopes, J.M., Soares, P. The mTOR signalling pathway in human cancer Int. J. Mol. Sci., 13 (2012),pp. 1886-1918
    [30]
    Provost, E., Weier, C.A., Leach, S.D. Multiple ribosomal proteins are expressed at high levels in developing zebrafish endoderm and are required for normal exocrine pancreas development Zebrafish, 10 (2013),pp. 161-169
    [31]
    Qin, W., Chen, Z., Zhang, Y. et al. Nom1 mediates pancreas development by regulating ribosome biogenesis in zebrafish PLoS One, 9 (2014)
    [32]
    Rosado, I.V., Cruz, D.L.J. RNA, 10 (2004),pp. 1073-1083
    [33]
    Rui, L. A link between protein translation and body weight J. Clin. Invest., 117 (2007),pp. 310-313
    [34]
    Shestopaloff, Y.K. Method for finding metabolic properties based on the general growth law. Liver examples. A general framework for biological modeling PLoS One, 9 (2014)
    [35]
    Sofer, A., Lei, K., Johannessen, C.M. et al. Regulation of mTOR and cell growth in response to energy stress by REDD1 Mol. Cell. Biol., 25 (2005),pp. 5834-5845
    [36]
    Strunk, B.S., Novak, M.N., Young, C.L. et al. A translation-like cycle is a quality control checkpoint for maturing 40S ribosome subunits Cell, 150 (2012),pp. 111-121
    [37]
    von Walden, F., Liu, C., Aurigemma, N. et al. mTOR signaling regulates myotube hypertrophy by modulating protein synthesis, rDNA transcription, and chromatin remodeling Am. J. Physiol. Cell. Physiol., 311 (2016),pp. 633-672
    [38]
    Wang, H., Zhao, L., Li, K. et al. Overexpression of ribosomal protein L15 is associated with cell proliferation in gastric cancer BMC Cancer, 6 (2006),p. 91
    [39]
    Wang, W., Nag, S., Zhang, X. et al. Ribosomal proteins and human diseases: pathogenesis, molecular mechanisms, and therapeutic implications Med. Res. Rev., 35 (2015),pp. 225-285
    [40]
    Westerfield, M.
    [41]
    Wullschleger, S., Loewith, R., Hall, M.N. TOR signaling in growth and metabolism Cell, 124 (2006),pp. 471-484
    [42]
    Yang, S., Aw, S., Chang, C. et al. Depletion of Bhmt elevates sonic hedgehog transcript level and increases β-cell number in zebrafish Endocrinology, 152 (2011),pp. 4706-4717
    [43]
    Yelick, P.C., Trainor, P.A. Ribosomopathies: global process, tissue specific defects Rare Dis., 3 (2015)
    [44]
    Zhou, J., Su, P., Wang, L. et al. mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells Proc. Natl. Acad. Sci. U. S. A., 106 (2009),pp. 7840-7845
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