HGNC Approved Gene Symbol: RPL24
Cytogenetic location: 3q12.3 Genomic coordinates (GRCh38): 3:101,681,091-101,686,718 (from NCBI)
The mammalian ribosome is composed of 4 RNA species (see 180450) and approximately 80 different proteins (see 180466).
During hybridization screening of a human choriocarcinoma cDNA library, Johnson (1993) identified, by chance, a cDNA encoding RPL24, which he called L30. He isolated additional RPL24 cDNAs by screening a normal human diploid fibroblast cell line cDNA library. The deduced sequence of the RPL24 protein is similar to those of the Saccharomyces cerevisiae ribosomal proteins L30A and L30B. RPL24 contains 157 amino acids and has a calculated pI of 9.6. The 5-prime untranslated region of the RPL24 cDNA contains a pyrimidine-rich sequence, a feature typical of mammalian ribosomal protein mRNAs. Northern blot analysis detected an approximately 700-bp RPL24 transcript in several human cell lines.
Barna et al. (2008) intercrossed Myc (190080) transgenic mice, in which Myc is overexpressed in the B-cell compartment (termed E(mu)-Myc/+) with L24 (Rpl24) heterozygous mice, which have overall decreased protein synthesis. By lowering the threshold of protein production in L24 heterozygote mice, the increased protein synthesis rates and cell size in the E(mu)-Myc heterozygote cells were restored to normal levels in the compound heterozygote mice. This effect suppressed the oncogenic potential of Myc in this context. Barna et al. (2008) concluded that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc-overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Barna et al. (2008) suggested that their findings revealed a mechanism that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation used to regulate the expression of selective mRNAs. Barna et al. (2008) showed that an aberrant increase in cap-dependent translation downstream of Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site (IRES)-dependent translation that is required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic-specific expression of the endogenous IRES-dependent form of Cdk11 (176873), which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in E(mu)-Myc/+ mice. When accurate translational control is reestablished in E(mu)-Myc/+ mice, genome instability is suppressed.
Barkic et al. (2009) found that RPL24 deficiency in human A549 cells triggered the p53 (TP53; 191170)-dependent checkpoint response.
Signer et al. (2014) compared protein synthesis in hematopoietic stem cells (HSCs) and restricted hematopoietic progenitors. Signer et al. (2014) found that the amount of protein synthesized per hour in HSCs in vivo was lower than in most other hematopoietic cells, even if differences in cell cycle status were controlled for or HSCs were forced to undergo self-renewing divisions. Reduced ribosome function in Rpl24(Bst/+) mice (see ANIMAL MODEL) further reduced protein synthesis in HSCs and impaired HSC function. Pten (601728) deletion increased protein synthesis in HSCs but also reduced HSC function. Rpl24(Bst/+) cell-autonomously rescued the effects of Pten deletion in HSCs, blocking the increase in protein synthesis, restoring HSC function, and delaying leukemogenesis. Signer et al. (2014) concluded that Pten deficiency depletes HSCs and promotes leukemia partly by increasing protein synthesis, and posited that either increased or decreased protein synthesis impairs HSC function.
By somatic cell hybrid and radiation hybrid mapping analyses, Kenmochi et al. (1998) mapped the human RPL24 gene to 3q.
'Belly spot and tail' (Bst) is a semidominant, homozygous lethal mutation in mouse that arose in the inbred strain C57BLKS. The mutation disrupts pigmentation, somitogenesis, and retinal cell fate determination. Heterozygous mice have a kinky tail, white feet, and a white spot at the ventral midline. Oliver et al. (2004) identified a deletion within the RPL24 riboprotein gene as the basis of Bst. The Bst mutation significantly impairs Rpl24 splicing and ribosome biogenesis. Bst heterozygous cells had decreased rates of protein synthesis and proliferation and were outcompeted by wildtype cells and C57BLKS-ROSA26 chimeras. This growth disadvantage in chimeras is similar to the classical cell competition effect observed in Drosophila 'Minute' somatic mosaics. Bacterial artificial chromosome and cDNA transgenes corrected the mutant phenotypes. Oliver et al. (2004) concluded that their findings established Bst as a mouse Minute and provided the first detailed characterization of a mammalian ribosomal protein mutation.
Barkic et al. (2009) showed that the Bst phenotype in Rpl24-deficient mice was largely due to aberrant upregulation of p53 during embryonic development.
Barkic, M., Crnomarkovic, S., Grabusic, K., Bogetic, I., Panic, L., Tamarut, S., Cokaric, M., Jeric, I., Vidak, S., Volarevic, S. The p53 tumor suppressor causes congenital malformations in Rpl24-deficient mice and promotes their survival. Molec. Cell. Biol. 29: 2489-2504, 2009. [PubMed: 19273598] [Full Text: https://doi.org/10.1128/MCB.01588-08]
Barna, M., Pusic, A., Zollo, O., Costa, M., Kondrashov, N., Rego, E., Rao, P. H., Ruggero, D. Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency. Nature 456: 971-975, 2008. [PubMed: 19011615] [Full Text: https://doi.org/10.1038/nature07449]
Johnson, K. R. Characterization of cDNA clones encoding the human homologue of Saccharomyces cerevisiae ribosomal protein L30. Gene 123: 283-285, 1993. [PubMed: 8428672] [Full Text: https://doi.org/10.1016/0378-1119(93)90139-t]
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]
Oliver, E. R., Saunders, T. L., Tarle, S. A., Glaser, T. Ribosomal protein L24 defect in belly spot and tail (Bst), a mouse Minute. Development 131: 3907-3920, 2004. [PubMed: 15289434] [Full Text: https://doi.org/10.1242/dev.01268]
Signer, R. A. J., Magee, J. A., Salic, A., Morrison, S. J. Haematopoietic stem cells require a highly regulated protein synthesis rate. Nature 509: 49-54, 2014. [PubMed: 24670665] [Full Text: https://doi.org/10.1038/nature13035]