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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 31, 2006 Accepted October 10, 2006 Impaired ribosome biogenesis in Diamond-Blackfan anemia Valerie Choesmel, Daniel Bacqueville, Jacques Rouquette, Jacqueline Noaillac-Depeyre, Sebastien Fribourg, Aurore Cretien, Thierry Leblanc, Gil Tchernia, Lydie DaCosta, and Pierre-Emmanuel Gleizes* CNRS / Universite Paul Sabatier, France Institut Europeen de Chimie et de Biologie, France Universite Paris XI, Institut Gustave Roussy, France Hopital Saint-Louis, France Hopital Bicetre, France * Corresponding author; email: gleizes{at}ibcg.biotoul.fr. 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: 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] K. Miyake, T. Utsugisawa, J. Flygare, T. Kiefer, I. Hamaguchi, J. Richter, and S. Karlsson Ribosomal Protein S19 Deficiency Leads to Reduced Proliferation and Increased Apoptosis but Does Not Affect Terminal Erythroid Differentiation in a Cell Line Model of Diamond-Blackfan Anemia Stem Cells, February 1, 2008; 26(2): 323 - 329. [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. Shimamura The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA Blood, September 1, 2007; 110(5): 1458 - 1465. [Abstract] [Full Text] [PDF] J. Flygare and S. Karlsson Diamond-Blackfan anemia: erythropoiesis lost in translation Blood, April 15, 2007; 109(8): 3152 - 3154. [Abstract] [Full Text] [PDF]

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