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The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus.
PLoS Genet 2015; 11(3):e1005018PG

Abstract

The production of ribosomes is ubiquitous and fundamental to life. As such, it is surprising that defects in ribosome biogenesis underlie a growing number of symptomatically distinct inherited disorders, collectively called ribosomopathies. We previously determined that the nucleolar protein, NOL11, is essential for optimal pre-rRNA transcription and processing in human tissue culture cells. However, the role of NOL11 in the development of a multicellular organism remains unknown. Here, we reveal a critical function for NOL11 in vertebrate ribosome biogenesis and craniofacial development. Nol11 is strongly expressed in the developing cranial neural crest (CNC) of both amphibians and mammals, and knockdown of Xenopus nol11 results in impaired pre-rRNA transcription and processing, increased apoptosis, and abnormal development of the craniofacial cartilages. Inhibition of p53 rescues this skeletal phenotype, but not the underlying ribosome biogenesis defect, demonstrating an evolutionarily conserved control mechanism through which ribosome-impaired craniofacial cells are removed. Excessive activation of this mechanism impairs craniofacial development. Together, our findings reveal a novel requirement for Nol11 in craniofacial development, present the first frog model of a ribosomopathy, and provide further insight into the clinically important relationship between specific ribosome biogenesis proteins and craniofacial cell survival.

Authors+Show Affiliations

Program in Vertebrate Developmental Biology, Departments of Pediatrics and Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.Departments of Genetics, Molecular Biophysics and Biochemistry, and Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.Program in Vertebrate Developmental Biology, Departments of Pediatrics and Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.Departments of Genetics, Molecular Biophysics and Biochemistry, and Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.Program in Vertebrate Developmental Biology, Departments of Pediatrics and Genetics, Yale University School of Medicine, New Haven, Connecticut, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25756904

Citation

Griffin, John N., et al. "The Ribosome Biogenesis Factor Nol11 Is Required for Optimal rDNA Transcription and Craniofacial Development in Xenopus." PLoS Genetics, vol. 11, no. 3, 2015, pp. e1005018.
Griffin JN, Sondalle SB, Del Viso F, et al. The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus. PLoS Genet. 2015;11(3):e1005018.
Griffin, J. N., Sondalle, S. B., Del Viso, F., Baserga, S. J., & Khokha, M. K. (2015). The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus. PLoS Genetics, 11(3), pp. e1005018. doi:10.1371/journal.pgen.1005018.
Griffin JN, et al. The Ribosome Biogenesis Factor Nol11 Is Required for Optimal rDNA Transcription and Craniofacial Development in Xenopus. PLoS Genet. 2015;11(3):e1005018. PubMed PMID: 25756904.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus. AU - Griffin,John N, AU - Sondalle,Samuel B, AU - Del Viso,Florencia, AU - Baserga,Susan J, AU - Khokha,Mustafa K, Y1 - 2015/03/10/ PY - 2014/07/31/received PY - 2015/01/22/accepted PY - 2015/3/11/entrez PY - 2015/3/11/pubmed PY - 2015/12/15/medline SP - e1005018 EP - e1005018 JF - PLoS genetics JO - PLoS Genet. VL - 11 IS - 3 N2 - The production of ribosomes is ubiquitous and fundamental to life. As such, it is surprising that defects in ribosome biogenesis underlie a growing number of symptomatically distinct inherited disorders, collectively called ribosomopathies. We previously determined that the nucleolar protein, NOL11, is essential for optimal pre-rRNA transcription and processing in human tissue culture cells. However, the role of NOL11 in the development of a multicellular organism remains unknown. Here, we reveal a critical function for NOL11 in vertebrate ribosome biogenesis and craniofacial development. Nol11 is strongly expressed in the developing cranial neural crest (CNC) of both amphibians and mammals, and knockdown of Xenopus nol11 results in impaired pre-rRNA transcription and processing, increased apoptosis, and abnormal development of the craniofacial cartilages. Inhibition of p53 rescues this skeletal phenotype, but not the underlying ribosome biogenesis defect, demonstrating an evolutionarily conserved control mechanism through which ribosome-impaired craniofacial cells are removed. Excessive activation of this mechanism impairs craniofacial development. Together, our findings reveal a novel requirement for Nol11 in craniofacial development, present the first frog model of a ribosomopathy, and provide further insight into the clinically important relationship between specific ribosome biogenesis proteins and craniofacial cell survival. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/25756904/The_ribosome_biogenesis_factor_Nol11_is_required_for_optimal_rDNA_transcription_and_craniofacial_development_in_Xenopus_ L2 - http://dx.plos.org/10.1371/journal.pgen.1005018 DB - PRIME DP - Unbound Medicine ER -