Article abstract

Nature Genetics 39, 486 - 495 (2007)
Published online: 11 March 2007 | doi:10.1038/ng1994

The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast

Tobias F Menne1,2,5, Beatriz Goyenechea1,2,5, Nuria Sánchez-Puig1,2, Chi C Wong1,2, Louise M Tonkin1,2, Philip J Ancliff3, Renée L Brost4, Michael Costanzo4, Charles Boone4 & Alan J Warren1,2

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.

  1. Medical Research Council (MRC) Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.
  2. The Department of Hematology, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK.
  3. Camelia Botnar Laboratories, Great Ormond Street Hospital, London WC1N 3JH, UK.
  4. Banting and Best Department of Medical Research and Department of Molecular Genetics and Microbiology, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada M5S 3E1, UK.
  5. These authors contributed equally to this work.

Correspondence to: Alan J Warren1,2 e-mail:


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