Alternative titles; symbols
HGNC Approved Gene Symbol: RPS14
Cytogenetic location: 5q33.1 Genomic coordinates (GRCh38): 5:150,442,635-150,449,739 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 5q33.1 | Macrocytic anemia, refractory, due to 5q deletion, somatic | 153550 | 3 |
The mammalian ribosome consists of 4 RNA species (see 180450) and approximately 80 different proteins. The ribosomal proteins are encoded by complex gene families that include at least 1 active intron-containing gene and multiple processed pseudogenes.
Dana and Wasmuth (1982) isolated interspecific hybrids between normal human leukocytes and a Chinese hamster ovary (CHO) cell line that had a mutation in the EMTB locus, leading to alteration of the 40S ribosomal protein S14 and, as a result, resistance to the protein synthesis inhibitor emetine. The cell line was also chromate-resistant due to a mutation in the CHR gene (118840) and temperature-sensitive because of a mutation in the leucyl-tRNA synthetase gene (LEUS; 151350). All 3 mutations were recessive in CHO cells. Therefore, human-CHO cell hybrids were emetine-sensitive, chromate-sensitive, and temperature-resistant.
By screening cDNAs derived from HeLa cell 10S to 12S mRNAs with a CHO Rps14 cDNA, Rhoads et al. (1986) isolated cDNAs encoding human RPS14. The deduced 151-amino acid human RPS14 protein is identical to CHO Rps14. The authors isolated human RPS14 genomic clones using human and CHO RPS14 cDNAs.
Chen et al. (1986) reported that the RPS14 gene appears to have been stringently conserved during evolution. They found high similarity between the C termini of mammalian RPS14 and yeast ribosomal protein 59; this region includes nucleotides that are mutated in emetine-resistant CHO cells (Rhoads and Roufa, 1985).
Rhoads et al. (1986) determined that the human RPS14 gene contains 5 exons and spans 5.9 kb.
All 3 genes related to emetine resistance isolated by Dana and Wasmuth (1982) appeared to be linked to the long arm of chromosome 2 in the Chinese hamster. Dana and Wasmuth (1982) showed that the genes for these 3 characteristics are carried by human chromosome 5. The results showed that synteny of the 3 genes has been long maintained in evolution. The EMTB locus, 1 of 3 genes that can be altered to give rise to the emetine-resistance phenotype, encodes ribosomal protein S14 (Madjar et al., 1982, Dana et al., 1985). Dana and Wasmuth (1982) subjected Chinese hamster-human interspecific hybrid cells, which contained human chromosome 5 and expressed the 4 syntenic genes LEUS, HEXB (606873), EMTB, and CHR, to selective conditions requiring them to retain the LEUS gene but lose either the EMTB or CHR gene. Using cytogenetic and biochemical analyses of spontaneous segregants, which arose primarily by terminal deletions of various portions of 5q, Dana and Wasmuth (1982) concluded that the order and specific locations of the linked genes are: LEUS, 5pter-5q1; HEXB, 5q13; EMTB, 5q23-5q35; and CHR, 5q35. Other ribosomal protein genes were mapped to chromosomes 8 and 17 by Nakamichi et al. (1986), using cDNA probes and hamster-human hybrid cells. The region of chromosome 8 carrying ribosomal protein genes was 8pter-q21.1. The ribosomal protein genes on chromosome 17 were on the long arm. Nakamichi et al. (1986) placed the RPS14 gene on the segment 5q23-q33.
Rhoads et al. (1986) mapped a DNA fragment derived from an intron of the RPS14 gene to 5q23-q33 using somatic cell hybrid DNAs, indicating that the functional RPS14 gene is located at this locus. Kenmochi et al. (1998) confirmed the mapping assignment reported by Rhoads et al. (1986).
Somatic RPS14 Haploinsufficiency Causes 5q Deletion Syndrome
The 5q- syndrome (153550) is a myelodysplastic syndrome subtype characterized by a defect in erythroid differentiation caused by recurring somatic deletion of a 1.5-Mb region on chromosome 5q containing 40 genes. While somatic chromosomal deletions in cancer have been thought to indicate the location of tumor suppressor genes whose biallelic inactivation results in cancer, no such biallelic inactivation had been found in patients with 5q- syndrome. Using an RNA-mediated interference-based approach, Ebert et al. (2008) found that partial loss of function of the ribosomal subunit protein RPS14 phenocopied the disease in normal hematopoietic progenitor cells. Forced expression of RPS14 rescued the disease phenotype in patient-derived bone marrow cells. In addition, the authors identified a block in the processing of preribosomal RNA in RPS14-deficient cells that is functionally equivalent to the defect in Diamond-Blackfan anemia (105650), linking the molecular pathophysiology of the 5q- syndrome (the somatic deletion of one allele of RPS14) to a congenital syndrome causing bone marrow failure. Ebert et al. (2008) concluded that the 5q- syndrome is caused by defects in ribosomal protein function and suggested that RNA interference screening is an effective strategy for identifying causal haploinsufficiency disease genes.
Chen, I.-T., Dixit, A., Rhoads, D. D., Roufa, D. J. Homologous ribosomal proteins in bacteria, yeast, and humans. Proc. Nat. Acad. Sci. 83: 6907-6911, 1986. [PubMed: 3529092] [Full Text: https://doi.org/10.1073/pnas.83.18.6907]
Dana, S., Wasmuth, J. J. Linkage of the leuS, emtB, and chr genes on chromosome 5 in humans and expression of human genes encoding protein synthetic components in human-Chinese hamster hybrids. Somat. Cell Genet. 8: 245-264, 1982. [PubMed: 9732752] [Full Text: https://doi.org/10.1007/BF01538680]
Dana, S., Wasmuth, J. J. Selective linkage disruption in human-Chinese hamster cell hybrids: deletion mapping of the leuS, hexB, emtB, and chr genes on human chromosome 5. Molec. Cell. Biol. 2: 1220-1228, 1982. [PubMed: 7177110] [Full Text: https://doi.org/10.1128/mcb.2.10.1220-1228.1982]
Dana, S. L., Chang, S., Wasmuth, J. J. Synthesis and incorporation of human ribosomal protein S14 into functional ribosomes in human-Chinese hamster cell hybrids containing human chromosome 5: human RPS14 gene is the structural gene for ribosomal protein S14. Somat. Cell Molec. Genet. 11: 625-631, 1985. [PubMed: 3865384] [Full Text: https://doi.org/10.1007/BF01534727]
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. Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature 451: 335-339, 2008. [PubMed: 18202658] [Full Text: https://doi.org/10.1038/nature06494]
Kenmochi, N., Kawaguchi, T., Rozen, S., Davis, E., Goodman, N., Hudson, T. J., Tanaka, T., Page, D. C. A map of 75 human ribosomal protein genes. Genome Res. 8: 509-523, 1998. [PubMed: 9582194] [Full Text: https://doi.org/10.1101/gr.8.5.509]
Madjar, J. J., Nielsen-Smith, K., Frahm, M., Roufa, D. Emetine resistance in Chinese hamster ovary cells is associated with an altered ribosomal protein S14 mRNA. Proc. Nat. Acad. Sci. 79: 1003-1007, 1982. [PubMed: 6122207] [Full Text: https://doi.org/10.1073/pnas.79.4.1003]
Nakamichi, N. N., Kao, F.-T., Wasmuth, J., Roufa, D. J. Ribosomal protein gene sequences map to human chromosomes 5, 8, and 17. Somat. Cell Molec. Genet. 12: 225-236, 1986. [PubMed: 3459254] [Full Text: https://doi.org/10.1007/BF01570781]
Rhoads, D. D., Dixit, A., Roufa, D. J. Primary structure of human ribosomal protein S14 and the gene that encodes it. Molec. Cell. Biol. 6: 2774-2783, 1986. [PubMed: 3785212] [Full Text: https://doi.org/10.1128/mcb.6.8.2774-2783.1986]
Rhoads, D. D., Roufa, D. J. Emetine resistance of Chinese hamster cells: structures of wild-type and mutant ribosomal protein S14 mRNAs. Molec. Cell. Biol. 5: 1655-1659, 1985. [PubMed: 3839563] [Full Text: https://doi.org/10.1128/mcb.5.7.1655-1659.1985]