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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1275-1283. Prepublished online as a Blood First Edition Paper on October 19, 2006; DOI 10.1182/blood-2006-07-038372. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-07-038372v1 109/3/1275    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Choesmel, V. Articles by Gleizes, P.-E. Search for Related Content PubMed PubMed Citation Articles by Choesmel, V. Articles by Gleizes, P.-E. Related Collections Red Cells Gene Expression Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Impaired ribosome biogenesis in Diamond-Blackfan anemia Valérie Choesmel1, Daniel Bacqueville1, Jacques Rouquette1, Jacqueline Noaillac-Depeyre1, Sébastien Fribourg2, Aurore Crétien3, Thierry Leblanc4,5, Gil Tchernia5, Lydie Da Costa3,5, and Pierre-Emmanuel Gleizes1 1 Laboratoire de Biologie Moléculaire des Eucaryotes (Unite Mixte de Recherche [UMR] 5099), Institut d'Exploration Fonctionnelle des Génomes (Institut Fédératif de Recherche [IFR] 109), Centre National de la Recherche Scientifique (CNRS) and Université Paul Sabatier, Toulouse, France; 2 Institut Européen de Chimie et Biologie, Institut National de la Santé et de la Recherche Médicale (INSERM) U386, Pessac, France; 3 INSERM U790, Université Paris XI, Institut Gustave Roussy (IGR), Villejuif, France; 4 Service d'oncologie-pédiatrie, Hôpital Saint-Louis, Paris, France; 5 Centre de référence des maladies génétiques de l'érythrocyte et de l'érythropoïèse, Hôpital Bicêtre, Le Kremlin-Bicêtre, France The gene encoding the ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia. The consequence of these mutations on the onset of the disease remains obscure. Here, we show that RPS19 plays an essential role in biogenesis of the 40S small ribosomal subunit in human cells. Knockdown of RPS19 expression by siRNAs impairs 18S rRNA synthesis and formation of 40S subunits and induces apoptosis in HeLa cells. Pre-rRNA processing is altered, which leads to an arrest in the maturation of precursors to the 18S rRNA. Under these conditions, pre-40S particles are not exported to the cytoplasm and accumulate in the nucleoplasm of the cells in perinuclear dots. Consistently, we find that ribosome biogenesis and nucleolar organization is altered in skin fibroblasts from DBA patients bearing mutations in the RPS19 gene. In addition, maturation of the 18S rRNA is also perturbed in cells from a patient bearing no RPS19-related mutation. These results support the hypothesis that DBA is directly related to a defect in ribosome biogenesis and indicate that yet to be discovered DBA-related genes may be involved in the synthesis of the ribosomal subunits. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Diamond-Blackfan anemia: "novel" mechanisms—ribosomes and the erythron Jeffrey M. Lipton Blood 2007 109: 850-851. [Full Text] [PDF] This article has been cited by other articles: N. Danilova, K. M. Sakamoto, and S. Lin Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family Blood, December 15, 2008; 112(13): 5228 - 5237. [Abstract] [Full Text] [PDF] A. Cretien, C. Hurtaud, H. Moniz, A. Proust, I. Marie, O. Wagner-Ballon, V. Choesmel, P.-E. Gleizes, T. Leblanc, J. Delaunay, et al. Study of the effects of proteasome inhibitors on ribosomal protein S19 (RPS19) mutants, identified in patients with Diamond-Blackfan anemia Haematologica, November 1, 2008; 93(11): 1627 - 1634. [Abstract] [Full Text] [PDF] T. Uechi, Y. Nakajima, A. Chakraborty, H. Torihara, S. Higa, and N. Kenmochi Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia Hum. Mol. Genet., October 15, 2008; 17(20): 3204 - 3211. [Abstract] [Full Text] [PDF] S. Robledo, R. A. Idol, D. L. Crimmins, J. H. Ladenson, P. J. Mason, and M. Bessler The role of human ribosomal proteins in the maturation of rRNA and ribosome production RNA, September 1, 2008; 14(9): 1918 - 1929. [Abstract] [Full Text] [PDF] A. Shimamura Diamond-Blackfan anemia: a new facet Blood, September 1, 2008; 112(5): 1552 - 1553. [Full Text] [PDF] J. E. Farrar, M. Nater, E. Caywood, M. A. McDevitt, J. Kowalski, C. M. Takemoto, C. C. Talbot Jr, P. Meltzer, D. Esposito, A. H. Beggs, et al. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia Blood, September 1, 2008; 112(5): 1582 - 1592. [Abstract] [Full Text] [PDF] J. M. Skarie and B. A. Link The Primary open-angle glaucoma gene WDR36 functions in ribosomal RNA processing and interacts with the p53 stress-response pathway Hum. Mol. Genet., August 15, 2008; 17(16): 2474 - 2485. [Abstract] [Full Text] [PDF] C.-R. Sihn, Y.-S. Lee, J.-S. Jeong, K. Park, and S. H. Kim CANu1, a novel nucleolar protein, accumulated on centromere in response to DNA damage Genes Cells, August 1, 2008; 13(8): 787 - 796. [Abstract] [Full Text] [PDF] V. Choesmel, S. Fribourg, A.-H. Aguissa-Toure, N. Pinaud, P. Legrand, H. T. Gazda, and P.-E. Gleizes Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder Hum. Mol. Genet., May 1, 2008; 17(9): 1253 - 1263. [Abstract] [Full Text] [PDF] Y. Coute, K. Kindbeiter, S. Belin, R. Dieckmann, L. Duret, L. Bezin, J.-C. Sanchez, and J.-J. Diaz ISG20L2, a Novel Vertebrate Nucleolar Exoribonuclease Involved in Ribosome Biogenesis Mol. Cell. Proteomics, March 1, 2008; 7(3): 546 - 559. [Abstract] [Full Text] [PDF] T. Pederson Ribosomal protein mutations in Diamond-Blackfan anemia: might they operate upstream from protein synthesis? FASEB J, November 1, 2007; 21(13): 3442 - 3445. [Abstract] [Full Text] [PDF] L. A. Gregory, A.-H. Aguissa-Toure, N. Pinaud, P. Legrand, P.-E. Gleizes, and S. Fribourg Molecular basis of Diamond Blackfan anemia: structure and function analysis of RPS19 Nucleic Acids Res., September 27, 2007; 35(17): 5913 - 5921. [Abstract] [Full Text] [PDF] S. Karlsson Connecting ribosomes with bone marrow failure Blood, September 1, 2007; 110(5): 1402 - 1402. [Full Text] [PDF] K. A. Ganapathi, K. M. Austin, C.-S. Lee, A. Dias, M. M. Malsch, R. Reed, and A. 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