The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast.
Nat Genet
; 39(4): 486-95, 2007 Apr.
Article
en En
| MEDLINE
| ID: mdl-17353896
The autosomal recessive disorder Shwachman-Diamond syndrome, characterized by bone marrow failure and leukemia predisposition, is caused by deficiency of the highly conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein. Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. Thus, our data link defective late 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ribosomas
/
Saccharomyces cerevisiae
/
Biosíntesis de Proteínas
/
Proteínas de Saccharomyces cerevisiae
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2007
Tipo del documento:
Article
Pais de publicación:
Estados Unidos