Format

Send to

Choose Destination
See comment in PubMed Commons below
Semin Hematol. 2011 Apr;48(2):89-96. doi: 10.1053/j.seminhematol.2011.02.005.

Diamond Blackfan anemia: ribosomal proteins going rogue.

Author information

1
Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292, USA. srellis@louisville.edu

Abstract

Within the decade following the demonstration that mutations in the RPS19 gene can lead to Diamond-Blackfan anemia (DBA), this disease has become a paradigm for an emerging group of pathologies linked to defects in ribosome biogenesis. DBA patients exhibit abnormal pre-rRNA maturation patterns and the majority bear mutations in one of several ribosomal protein genes that encode structural components of the ribosome essential for the correct assembly of the ribosomal subunits. Extensive study of the most frequently mutated gene, RPS19, has shown that mutations prevent the assembly of the ribosomal protein into forming pre-ribosomal particles. This defect in ribosome production triggers nucleolar stress pathways, the activation of which appears to be central to pathophysiological mechanisms. Why mutations in ribosomal protein genes so strongly and specifically affect erythropoiesis in DBA remains a challenging question, especially given the fact that defects in genes encoding nonstructural ribosome biogenesis factors have been shown to cause diseases other than DBA. A major problem in understanding the pathophysiological mechanisms in DBA remains the lack of a suitable animal model. Despite this, considerable strides have been made over that past few years demonstrating that several factors involved in the synthesis of ribosomes are targets of disease-causing mutations.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center