Specific Role for Yeast Homologs of the Diamond Blackfan Anemia-associated Rps19 Protein in Ribosome Synthesis

J Biol Chem. 2005 Nov 18;280(46):38177-85. doi: 10.1074/jbc.M506916200. Epub 2005 Sep 12.


Approximately 25% of cases of Diamond Blackfan anemia, a severe hypoplastic anemia, are linked to heterozygous mutations in the gene encoding ribosomal protein S19 that result in haploinsufficiency for this protein. Here we show that deletion of either of the two genes encoding Rps19 in yeast severely affects the production of 40 S ribosomal subunits. Rps19 is an essential protein that is strictly required for maturation of the 3'-end of 18 S rRNA. Depletion of Rps19 results in the accumulation of aberrant pre-40 S particles retained in the nucleus that fail to associate with pre-ribosomal factors involved in late maturation steps, including Enp1, Tsr1, and Rio2. When introduced in yeast Rps19, amino acid substitutions found in Diamond Blackfan anemia patients induce defects in the processing of the pre-rRNA similar to those observed in cells under-expressing Rps19. These results uncover a pivotal role of Rps19 in the assembly and maturation of the pre-40 S particles and demonstrate for the first time the effect of Diamond Blackfan anemia-associated mutations on the function of Rps19, strongly connecting the pathology to ribosome biogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Anemia, Diamond-Blackfan / metabolism*
  • Blotting, Northern
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cell Survival
  • Fungal Proteins / metabolism
  • Galactose / chemistry
  • Gene Deletion
  • Heterozygote
  • Humans
  • Immunoprecipitation
  • In Situ Hybridization, Fluorescence
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Mutation, Missense
  • Nuclear Proteins / metabolism
  • Nucleic Acid Hybridization
  • Plasmids / metabolism
  • Polyribosomes / metabolism
  • Protein Binding
  • Protein Serine-Threonine Kinases
  • RNA / chemistry
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal, 18S / genetics
  • Ribosomal Proteins / metabolism
  • Ribosomal Proteins / physiology*
  • Ribosomes / chemistry
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sepharose / chemistry
  • Sequence Homology, Amino Acid
  • Time Factors


  • ENP1 protein, S cerevisiae
  • Fungal Proteins
  • Nuclear Proteins
  • RNA, Ribosomal
  • RNA, Ribosomal, 18S
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • TSR1 protein, Yarrowia lipolytica
  • ribosomal protein S19
  • RNA
  • Sepharose
  • Protein Serine-Threonine Kinases
  • Rio2 protein, S cerevisiae
  • Galactose