Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production.

Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Research Abstract Details 

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Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Abstract Text:

Rachel A Idol,Sara Robledo,Hong-Yan Du,Dan L Crimmins,David B Wilson,Jack H Ladenson,Monica Bessler,Philip J Mason,

The gene encoding the small subunit ribosomal protein 19 (RPS19) is mutated in about 25% of cases of the bone marrow failure syndrome Diamond Blackfan Anemia (DBA), a childhood disease characterized by failure of red cell production. In these cases DBA is inherited as an autosomal dominant trait and RPS19 haploinsufficiency is thought to cause the disease. To study the molecular pathogenesis of DBA we used siRNA to decrease the level of RPS19 in two human cell lines, HeLa cells and U-2 OS osteosarcoma cells. Cells with reduced RPS19 levels showed a dramatic reduction in the amounts of small 40S ribosome subunits and mature 80S ribosomes and an excess of large 60S subunits. These cells were defective in 18S rRNA production and accumulated 21S and 20S nuclear pre-rRNA molecules, suggesting that RPS19 is required for specific steps in rRNA processing. RPS19 depletion produced a reduction in steady-state levels of RPS6 and RPS16 via a post-transcriptional mechanism while the levels of RPL7 and RPL26 were unaltered, indicating that levels of ribosomal proteins are determined by subunit assembly. This has interesting implications for the pathogenesis of DBA suggesting that deficiency of any of the RPS proteins might have a similar effect and thus may be responsible for causing DBA. Finally in cell lines from DBA patients with mutations we find increased levels of 21S rRNA precursors but no abnormality in the ribosome profile on sucrose gradients or in the steady-state levels of RPS19 suggesting that some cells can partially compensate for the loss of one allele of RPS19. We conclude that defects in ribosome biogenesis may underlie the pathology of Diamond Blackfan Anemia.

Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Publishing Authors By Initials

RA Idol,S Robledo,HY Du,DL Crimmins,DB Wilson,JH Ladenson,M Bessler,PJ Mason,

For similar cells: cellular structures: intracellular space: cytoplasm: cytoplasmic structures: organelles: ribosomes research abstracts see: cells: cellular structures: intracellular space: cytoplasm: cytoplasmic structures: organelles: ribosomes research

PUBMED ID PMID:

MEDLINE DATE: 2007 Jul-Aug

Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Blood cells, molecules & diseases

VOLUME: 39

Page Numbers: 35-43

Journal Abbreviation: Blood Cells Mol. Dis.

ISSN: 1079-9796

DAY: 21

MONTH: 03

YEAR: 2007

Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9509932

Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Keywords Mesh Terms:

KEYWORDS: Ribosomes

MESH TERMS: metabolism

Chemical & Substance for Abstract: Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Information

Substance Name: ribosomal protein S19

Registry Number: 0

Grant and Affiliation Information for Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production.

AFFILIATION: Department of Internal Medicine, Division of Hematology, Division of Laboratory Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: R21 DK075443-01

ACRONYM: DK

MEDLINETA: Blood Cells Mol Dis

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