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Ribosomopathies Through a Diamond Lens

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Bone Marrow Failure

Part of the book series: Pediatric Oncology ((PEDIATRICO))

Abstract

There are an increasing number of human disorders linked to defects in ribosome synthesis collectively known as ribosomopathies. Here we use the prototypical ribosomopathy, Diamond-Blackfan anemia, to explore relationships between the structure of the ribosome, its biogenesis, and the molecular mechanisms that contribute to disease pathology. Other ribosomopathies are discussed as they relate to the genes affected and pathophysiological mechanisms involved in Diamond-Blackfan anemia. The recent finding that several genes affecting ribosome biogenesis are somatically mutated in human tumors implies that understanding the molecular mechanisms underlying this rare group of disorders will likely have much broader implications.

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References

  • Amsterdam A et al (2004) Many ribosomal protein genes are cancer genes in zebrafish. PLoS Biol 2(5):E139

    Article  Google Scholar 

  • Angrisani A et al (2014) Human dyskerin: beyond telomeres. Biol Chem 395(6):593–610

    Article  CAS  Google Scholar 

  • Ban N et al (2014) A new system for naming ribosomal proteins. Curr Opin Struct Biol 24:165–169

    Article  CAS  Google Scholar 

  • Bellodi C et al (2010) Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis. Cancer Res 70(14):6026–6035

    Article  CAS  Google Scholar 

  • Chen J, Guo K, Kastan MB (2012) Interactions of nucleolin and ribosomal protein L26 (RPL26) in translational control of human p53 mRNA. J Biol Chem 287(20):16467–16476

    Article  CAS  Google Scholar 

  • Choesmel V et al (2007) Impaired ribosome biogenesis in Diamond-Blackfan anemia. Blood 109(3):1275–1283

    Article  CAS  Google Scholar 

  • Danilova N, Gazda HT (2015) Ribosomopathies: how a common root can cause a tree of pathologies. Dis Model Mech 8(9):1013–1026

    Article  CAS  Google Scholar 

  • Danilova N, Sakamoto KM, Lin S (2008) Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family. Blood 112(13):5228–5237

    Article  CAS  Google Scholar 

  • De Keersmaecker K et al (2013) Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nat Genet 45(2):186–190

    Article  Google Scholar 

  • Donati G et al (2013) 5S ribosomal RNA is an essential component of a nascent ribosomal precursor complex that regulates the Hdm2-p53 checkpoint. Cell Rep 4(1):87–98

    Article  CAS  Google Scholar 

  • Dutt S et al (2011) Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood 117(9):2567–2576

    Article  CAS  Google Scholar 

  • Ebert BL et al (2008) Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature 451(7176):335–339

    Article  CAS  Google Scholar 

  • Ellis SR, Gleizes PE (2011) Diamond Blackfan anemia: ribosomal proteins going rogue. Semin Hematol 48(2):89–96

    Article  CAS  Google Scholar 

  • Farrar JE et al (2014) Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis. Am J Hematol 89(10):985–991

    Article  CAS  Google Scholar 

  • Flygare J et al (2007) Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits. Blood 109(3):980–986

    Article  CAS  Google Scholar 

  • Fujii K et al (2012) 40S subunit dissociation and proteasome-dependent RNA degradation in nonfunctional 25S rRNA decay. EMBO J 31(11):2579–2589

    Article  CAS  Google Scholar 

  • Fumagalli S et al (2009) Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction. Nat Cell Biol 11(4):501–508

    Article  CAS  Google Scholar 

  • Gamalinda M, Woolford JL Jr (2014) Deletion of L4 domains reveals insights into the importance of ribosomal protein extensions in eukaryotic ribosome assembly. RNA 20(11):1725–1731

    Article  CAS  Google Scholar 

  • Gazda HT et al (2008) Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet 83(6):769–780

    Article  CAS  Google Scholar 

  • Goudarzi KM, Lindstrom MS (2016) Role of ribosomal protein mutations in tumor development (Review). Int J Oncol 48(4):1313–1324

    Article  CAS  Google Scholar 

  • Gripp KW et al (2014) Diamond-Blackfan anemia with mandibulofacial dystostosis is heterogeneous, including the novel DBA genes TSR2 and RPS28. Am J Med Genet A 164A(9):2240–2249

    Article  Google Scholar 

  • Held WA et al (1974) Assembly mapping of 30 S ribosomal proteins from Escherichia coli. Further studies. J Biol Chem 249(10):3103–3111

    CAS  PubMed  Google Scholar 

  • Horos R et al (2012) Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts. Blood 119(1):262–272

    Article  CAS  Google Scholar 

  • Jaako P et al (2015) Disruption of the 5S RNP-Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia. Leukemia 29(11):2221–2229

    Article  CAS  Google Scholar 

  • Kazerounian S et al (2016) Development of Soft Tissue Sarcomas in Ribosomal Proteins L5 and S24 Heterozygous Mice. J Cancer 7(1):32–36

    Article  CAS  Google Scholar 

  • Khatter H et al (2015) Structure of the human 80S ribosome. Nature 520(7549):640–645

    Article  CAS  Google Scholar 

  • Kim TH, Leslie P, Zhang Y (2014) Ribosomal proteins as unrevealed caretakers for cellular stress and genomic instability. Oncotarget 5(4):860–871

    Article  Google Scholar 

  • Kondrashov N et al (2011) Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. Cell 145(3):383–397

    Article  CAS  Google Scholar 

  • de la Cruz J, Karbstein K, Woolford JL Jr (2015) Functions of ribosomal proteins in assembly of eukaryotic ribosomes in vivo. Annu Rev Biochem 84:93–129

    Article  Google Scholar 

  • Liu JM, Ellis SR (2006) Ribosomes and marrow failure: coincidental association or molecular paradigm? Blood 107(12):4583–4588

    Article  CAS  Google Scholar 

  • Ludwig LS et al (2014) Altered translation of GATA1 in Diamond-Blackfan anemia. Nat Med 20(7):748–753

    Article  CAS  Google Scholar 

  • Marechal V et al (1994) The ribosomal L5 protein is associated with mdm-2 and mdm-2-p53 complexes. Mol Cell Biol 14(11):7414–7420

    Article  CAS  Google Scholar 

  • Melnikov S et al (2012) One core, two shells: bacterial and eukaryotic ribosomes. Nat Struct Mol Biol 19(6):560–567

    Article  CAS  Google Scholar 

  • Menne TF et al (2007) The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nat Genet 39(4):486–495

    Article  CAS  Google Scholar 

  • Moore JBt et al (2010) Distinct ribosome maturation defects in yeast models of Diamond-Blackfan anemia and Shwachman-Diamond syndrome. Haematologica 95(1):57–64

    Article  CAS  Google Scholar 

  • Moreland JL et al (2005) The Molecular Biology Toolkit (MBT): a modular platform for developing molecular visualization applications. BMC Bioinformatics 6:21

    Article  Google Scholar 

  • Nicolas E et al (2016) Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress. Nat Commun 7:11390

    Article  Google Scholar 

  • O’Donohue MF et al (2010) Functional dichotomy of ribosomal proteins during the synthesis of mammalian 40S ribosomal subunits. J Cell Biol 190(5):853–866

    Article  Google Scholar 

  • Pestov DG, Strezoska Z, Lau LF (2001) Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: effects of nucleolar protein Bop1 on G(1)/S transition. Mol Cell Biol 21(13):4246–4255

    Article  CAS  Google Scholar 

  • Quarello P et al (2016) Ribosomal RNA analysis in the diagnosis of Diamond-Blackfan Anaemia. Br J Haematol 172(5):782–785

    Article  CAS  Google Scholar 

  • Rao S et al (2012) Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood 120(18):3764–3773

    Article  CAS  Google Scholar 

  • Sankaran VG et al (2012) Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. J Clin Invest 122(7):2439–2443

    Article  CAS  Google Scholar 

  • Sondalle SB, Baserga SJ (2014) Human diseases of the SSU processome. Biochim Biophys Acta 1842(6):758–764

    Article  CAS  Google Scholar 

  • Stewart MJ, Denell R (1993) Mutations in the Drosophila gene encoding ribosomal protein S6 cause tissue overgrowth. Mol Cell Biol 13(4):2524–2535

    Article  CAS  Google Scholar 

  • Sulima SO et al (2014) Bypass of the pre-60S ribosomal quality control as a pathway to oncogenesis. Proc Natl Acad Sci U S A 111(15):5640–5645

    Article  CAS  Google Scholar 

  • Townsley DM, Dumitriu B, Young NS (2014) Bone marrow failure and the telomeropathies. Blood 124(18):2775–2783

    Article  CAS  Google Scholar 

  • Vlachos A et al (2012) Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. Blood 119(16):3815–3819

    Article  CAS  Google Scholar 

  • Weis F et al (2015) Mechanism of eIF6 release from the nascent 60S ribosomal subunit. Nat Struct Mol Biol 22(11):914–919

    Article  CAS  Google Scholar 

  • Xu X, Xiong X, Sun Y (2016) The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity. Sci China Life Sci 59(7):656–672

    Article  CAS  Google Scholar 

  • Yang Z et al (2016) Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome. Sci Transl Med 8(338):338ra67

    Article  Google Scholar 

  • Yelick PC, Trainor PA (2015) Ribosomopathies: global process, tissue specific defects. Rare Dis 3(1):e1025185

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Health Sciences, University of Eastern Piedmont, Novara, Italy

    Anna Aspesi

  2. Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, USA

    Steven R. Ellis

Authors
  1. Anna Aspesi
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  2. Steven R. Ellis
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Corresponding author

Correspondence to Steven R. Ellis .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA

    Gary M. Kupfer

  2. Department of Pediatrics, George Washington University, Washington, DC, USA

    Gregory H. Reaman

  3. Medpace, Cincinnati, OH, USA

    Franklin O. Smith

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Aspesi, A., Ellis, S.R. (2018). Ribosomopathies Through a Diamond Lens. In: Kupfer, G., Reaman, G., Smith, F. (eds) Bone Marrow Failure. Pediatric Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-61421-2_5

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  • DOI: https://doi.org/10.1007/978-3-319-61421-2_5

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-61420-5

  • Online ISBN: 978-3-319-61421-2

  • eBook Packages: MedicineMedicine (R0)

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