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Cited by 928

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Identification of RPS14 as a 5q- syndrome gene by RNA interference screen

Open access
Ebert, Benjamin L., Pretz, Jennifer, Bosco, Jocelyn, Chang, Cindy Y., Tamayo, Pablo, Galili, Naomi, Raza, Azra, Root, David E., Attar, Eyal, Ellis, Steven R., Golub, Todd R.·2008·Nature
DOI 10.1038/nature06494
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Abstract

Somatic chromosomal deletions in cancer are thought to indicate the location of tumour suppressor genes, by which a complete loss of gene function occurs through biallelic deletion, point mutation or epigenetic silencing, thus fulfilling Knudson’s two-hit hypothesis. In many recurrent deletions, however, such biallelic inactivation has not been found. One prominent example is the 5q- syndrome, a subtype of myelodysplastic syndrome characterized by a defect in erythroid differentiation. Here we describe an RNA-mediated interference (RNAi)-based approach to discovery of the 5q- disease gene. We found that partial loss of function of the ribosomal subunit protein RPS14 phenocopies the disease in normal haematopoietic progenitor cells, and also that forced expression of RPS14 rescues the disease phenotype in patient-derived bone marrow cells. In addition, we identified a block in the processing of pre-ribosomal RNA in RPS14-deficient cells that is functionally equivalent to the defect in Diamond–Blackfan anaemia, linking the molecular pathophysiology of the 5q- syndrome to a congenital syndrome causing bone marrow failure. These results indicate that the 5q- syndrome is caused by a defect in ribosomal protein function and suggest that RNAi screening is an effective strategy for identifying causal haploinsufficiency disease genes.

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Research works printed but not linked: 28

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Cited by

Metadata

Authors
Ebert, B. L., Pretz, J., Bosco, J., Chang, C. Y., Tamayo, P., Galili, N., Raza, A., Root, D. E., Attar, E., Ellis, S. R., & Golub, T. R.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2008-01
Volume
451
Issue
7176
Pages
335-339
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature06494
OpenAlex
W2121533623
Cited by
928
References
2
FWCI
63.35
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

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