Impaired ribosome biogenesis in Diamond-Blackfan anemia

被引:172
作者
Choesmel, Valerie
Bacqueville, Daniel
Rouquette, Jacques
Noaillac-Depeyre, Jacqueline
Fribourg, Sebastien
Cretien, Aurore
Leblanc, Thierry
Tchernia, Gil
Da Costa, Lydie
Gleizes, Pierre-Emmanuel
机构
[1] CNRS, UMR 5099, Inst Explorat Fonct Genomes, IFR 109,LBME, F-31062 Toulouse, France
[2] Univ Toulouse 3, F-31062 Toulouse, France
[3] INSERM, Inst Europeen Chim & Biol, U386, Pessac, France
[4] Univ Paris 11, INSERM, IGR, U790, Villejuif, France
[5] Hop St Louis, Serv Oncol Pediat, Paris, France
[6] Hop Bicetre, Ctr Reference Malad Genet Erythrocyte & Erythropo, Le Kremlin Bicetre, France
关键词
D O I
10.1182/blood-2006-07-038372
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1275 / 1283
页数:9
相关论文
共 39 条
[31]   Nuclear export and cytoplasmic processing of precursors to the 40S ribosomal subunits in mammalian cells [J].
Rouquette, J ;
Choesmel, V ;
Gleizes, PE .
EMBO JOURNAL, 2005, 24 (16) :2862-2872
[32]   Spatial preservation of nuclear chromatin architecture during three-dimensional fluorescence in situ hybridization (3D-FISH) [J].
Solovei, I ;
Cavallo, A ;
Schermelleh, L ;
Jaunin, F ;
Scasselati, C ;
Cmarko, D ;
Cremer, C ;
Fakan, S ;
Cremer, T .
EXPERIMENTAL CELL RESEARCH, 2002, 276 (01) :10-23
[33]   Fibroblast growth factor-2 interacts with free ribosomal protein S19 [J].
Soulet, F ;
Al Saati, T ;
Roga, S ;
Amalric, F ;
Bouche, G .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 289 (02) :591-596
[34]   Inactivation of S6 ribosomal protein gene in T lymphocytes activates a p53-dependent checkpoint response [J].
Sulic, S ;
Panic, L ;
Barkic, M ;
Mercep, M ;
Uzelac, M ;
Volarevic, S .
GENES & DEVELOPMENT, 2005, 19 (24) :3070-3082
[35]   Processing of 20S pre-rRNA to 18S ribosomal RNA in yeast requires Rrp10p, an essential non-ribosomal cytoplasmic protein [J].
Vanrobays, E ;
Gleizes, PE ;
Bousquet-Antonelli, C ;
Noaillac-Depeyre, J ;
Caizergues-Ferrer, M ;
Gélugne, JP .
EMBO JOURNAL, 2001, 20 (15) :4204-4213
[36]  
Willig TN, 1999, BLOOD, V94, P4294
[37]   Identification of new prognosis factors from the clinical and epidemiologic analysis of a registry of 229 Diamond-Blackfan anemia patients [J].
Willig, TN ;
Niemeyer, CM ;
Leblanc, T ;
Tiemann, C ;
Robert, A ;
Budde, J ;
Lambiliotte, A ;
Kohne, E ;
Souillet, G ;
Eber, S ;
Stephan, JL ;
Girot, R ;
Bordigoni, P ;
Cornu, G ;
Blanche, S ;
Guillard, JM ;
Mohandas, N ;
Tchernia, G .
PEDIATRIC RESEARCH, 1999, 46 (05) :553-561
[38]   Diamond-Blackfan anemia [J].
Willig, TN ;
Gazda, H ;
Sieff, CA .
CURRENT OPINION IN HEMATOLOGY, 2000, 7 (02) :85-94
[39]   Extraribosomal functions of ribosomal proteins [J].
Wool, IG .
TRENDS IN BIOCHEMICAL SCIENCES, 1996, 21 (05) :164-165