Distinct ribosome maturation defects in yeast models of Diamond-Blackfan anemia and Shwachman-Diamond syndrome.

Abstract

BACKGROUND:

Diamond-Blackfan anemia and Shwachman-Diamond syndrome are inherited bone marrow failure syndromes linked to defects in ribosome synthesis. The purpose of this study was to determine whether yeast models for Diamond-Blackfan anemia and Shwachman-Diamond syndrome differed in the mechanism by which ribosome synthesis was affected.

DESIGN AND METHODS:

Northern blotting, pulse-chase analysis, and polysome profiling were used to study ribosome synthesis in yeast models. Localization of 60S ribosomal subunits was assessed using RPL25eGFP.

RESULTS:

Relative to wild-type controls, each disease model showed defects in 60S subunit maturation, but with distinct underlying mechanisms. In the model of Diamond-Blackfan anemia, 60S subunit maturation was disrupted at a relatively early stage with abortive complexes subject to rapid degradation. 5S ribosomal RNA, unlike other large subunit ribosomal RNA in this model, accumulated as an extra-ribosomal species. In contrast, subunit maturation in the Shwachman-Diamond syndrome model was affected at a later step, giving rise to relatively stable pre-60S particles with associated 5S ribosomal RNA retained in the nucleus. Conclusions These differences between the yeast Diamond-Blackfan anemia and Shwachman-Diamond syndrome models have implications for signaling mechanisms linking abortive ribosome assembly to cell fate decisions and may contribute to the divergent clinical presentations of Diamond-Blackfan anemia and Shwachman-Diamond syndrome.

• Authors: Joseph B Moore 4th, Jason E Farrar, Robert J Arceci, Johnson M Liu, Steven R Ellis
• Journal: Haematologica (Haematologica) Vol. 95 Issue 1 Pg. 57-64 (Jan 2010) ISSN: 1592-8721 [Electronic] Italy
• PMID: 19713223 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Ribosomal Proteins
• Saccharomyces cerevisiae Proteins
• ribosomal protein L11
• ribosomal protein L25
• ribosomal protein L5, human

Topics

• Anemia, Diamond-Blackfan (genetics, metabolism, pathology)
• Animals
• Disease Models, Animal
• Humans
• Models, Biological
• Mutation
• Ribosomal Proteins (genetics)
• Ribosome Subunits, Large, Eukaryotic (genetics)
• Ribosomes (genetics, pathology)
• Saccharomyces cerevisiae Proteins (biosynthesis, genetics)