Journal Article

Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder

Valérie Choesmel, Sébastien Fribourg, Almass-Houd Aguissa-Touré, Noël Pinaud, Pierre Legrand, Hanna T. Gazda and Pierre-Emmanuel Gleizes

in Human Molecular Genetics

Volume 17, issue 9, pages 1253-1263
Published in print May 2008 | ISSN: 0964-6906
Published online January 2008 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddn015
Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder

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Diamond-Blackfan anemia (DBA) is a rare congenital disease affecting erythroid precursor differentiation. DBA is emerging as a paradigm for a new class of pathologies potentially linked to disorders in ribosome biogenesis. Three genes encoding ribosomal proteins have been associated to DBA: after RPS19, mutations in genes RPS24 and RPS17 were recently identified in a fraction of the patients. Here, we show that cells from patients carrying mutations in RPS24 have defective pre-rRNA maturation, as in the case of RPS19 mutations. However, in contrast to RPS19 involvement in the maturation of the internal transcribed spacer 1, RPS24 is required for processing of the 5′ external transcribed spacer. Remarkably, epistasis experiments with small interfering RNAs indicate that the functions of RPS19 and RPS24 in pre-rRNA processing are connected. Resolution of the crystal structure of RPS24e from the archeon Pyroccocus abyssi reveals domains of RPS24 potentially involved in interactions with pre-ribosomes. Based on these data, we discuss the impact of RPS24 mutations and speculate that RPS19 and RPS24 cooperate at a particular stage of ribosome biogenesis connected to a cell cycle checkpoint, thus affecting differentiation of erythroid precursors as well as developmental processes.

Journal Article.  6305 words.  Illustrated.

Subjects: Genetics and Genomics

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