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
Angrisani A et al (2014) Human dyskerin: beyond telomeres. Biol Chem 395(6):593–610
Ban N et al (2014) A new system for naming ribosomal proteins. Curr Opin Struct Biol 24:165–169
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
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
Choesmel V et al (2007) Impaired ribosome biogenesis in Diamond-Blackfan anemia. Blood 109(3):1275–1283
Danilova N, Gazda HT (2015) Ribosomopathies: how a common root can cause a tree of pathologies. Dis Model Mech 8(9):1013–1026
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
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
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
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
Ebert BL et al (2008) Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature 451(7176):335–339
Ellis SR, Gleizes PE (2011) Diamond Blackfan anemia: ribosomal proteins going rogue. Semin Hematol 48(2):89–96
Farrar JE et al (2014) Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis. Am J Hematol 89(10):985–991
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
Fujii K et al (2012) 40S subunit dissociation and proteasome-dependent RNA degradation in nonfunctional 25S rRNA decay. EMBO J 31(11):2579–2589
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
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
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
Goudarzi KM, Lindstrom MS (2016) Role of ribosomal protein mutations in tumor development (Review). Int J Oncol 48(4):1313–1324
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
Held WA et al (1974) Assembly mapping of 30 S ribosomal proteins from Escherichia coli. Further studies. J Biol Chem 249(10):3103–3111
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
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
Kazerounian S et al (2016) Development of Soft Tissue Sarcomas in Ribosomal Proteins L5 and S24 Heterozygous Mice. J Cancer 7(1):32–36
Khatter H et al (2015) Structure of the human 80S ribosome. Nature 520(7549):640–645
Kim TH, Leslie P, Zhang Y (2014) Ribosomal proteins as unrevealed caretakers for cellular stress and genomic instability. Oncotarget 5(4):860–871
Kondrashov N et al (2011) Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. Cell 145(3):383–397
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
Liu JM, Ellis SR (2006) Ribosomes and marrow failure: coincidental association or molecular paradigm? Blood 107(12):4583–4588
Ludwig LS et al (2014) Altered translation of GATA1 in Diamond-Blackfan anemia. Nat Med 20(7):748–753
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
Melnikov S et al (2012) One core, two shells: bacterial and eukaryotic ribosomes. Nat Struct Mol Biol 19(6):560–567
Menne TF et al (2007) The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nat Genet 39(4):486–495
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
Moreland JL et al (2005) The Molecular Biology Toolkit (MBT): a modular platform for developing molecular visualization applications. BMC Bioinformatics 6:21
Nicolas E et al (2016) Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress. Nat Commun 7:11390
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
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
Quarello P et al (2016) Ribosomal RNA analysis in the diagnosis of Diamond-Blackfan Anaemia. Br J Haematol 172(5):782–785
Rao S et al (2012) Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood 120(18):3764–3773
Sankaran VG et al (2012) Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. J Clin Invest 122(7):2439–2443
Sondalle SB, Baserga SJ (2014) Human diseases of the SSU processome. Biochim Biophys Acta 1842(6):758–764
Stewart MJ, Denell R (1993) Mutations in the Drosophila gene encoding ribosomal protein S6 cause tissue overgrowth. Mol Cell Biol 13(4):2524–2535
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
Townsley DM, Dumitriu B, Young NS (2014) Bone marrow failure and the telomeropathies. Blood 124(18):2775–2783
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
Weis F et al (2015) Mechanism of eIF6 release from the nascent 60S ribosomal subunit. Nat Struct Mol Biol 22(11):914–919
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
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
Yelick PC, Trainor PA (2015) Ribosomopathies: global process, tissue specific defects. Rare Dis 3(1):e1025185
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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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