Alternative titles; symbols
HGNC Approved Gene Symbol: RPL22
Cytogenetic location: 1p36.31 Genomic coordinates (GRCh38): 1:6,185,020-6,199,595 (from NCBI)
Shu-Nu et al. (2000) reported that the 128-amino acid human RPL22 protein has a 9-amino acid hydrophobic N-terminal domain, followed by a central I domain, which contains KRYLK and KKYLK motifs, and a 9-amino acid C-terminal domain. Epitope-tagged RPL22 localized to the nucleolus of transfected HeLa cells.
By PCR of a human-rodent somatic cell hybrid panel, radiation hybrid analysis, and genomic sequence analysis, Uechi et al. (2001) mapped the RPL22 gene to chromosome 1p36.3. They stated that the RPL22 copy reported by Nucifora et al. (1993) and Nucifora and Rowley (1995) on chromosome 3q26 (see HISTORY) is a processed pseudogene.
By deletion analysis of RPL22, Shu-Nu et al. (2000) identified a KKKK nuclear localization signal following the N-terminal domain, as well as a KKYLKK nucleolar entry motif in the I domain. Yeast 2-hybrid analysis revealed that the isolated N terminus of RPL22 interacted with the isolated C terminus of RPL22. RPL22 lacking these domains did not target to the nucleolus.
Using microarray-based copy number analysis, Rao et al. (2012) found that RPL22 was monoallelically inactivated in approximately 10% of primary human samples of T-cell acute lymphoblastic leukemia (T-ALL; see 613065).
Rao et al. (2012) reported that Rpl22-null mice were viable, fertile, and grossly normal, but that they had a specific block in the development of alpha-beta lineage T cells. Using transgenic mice expressing constitutively active Akt2 (164731), a mouse model of T-ALL, the authors found that haploinsufficiency of Rpl22 accelerated the development of thymic lymphoma. Rpl22-knockdown mouse embryonic fibroblasts (MEFs) revealed increased expression of the stemness factor Lin28b (611044). Knockdown of Lin28b via short hairpin RNA reduced growth rate and colony formation in RPL22-null MEFs. Inhibition of NF-kappa-B (see RELA, 164014) signaling or knockdown of Rela blocked induction of Lin28b in Rpl22-null MEFs. Since Lin28 is a negative regulator of microRNAs of the Let7 family (see MIRLET7A1, 605386), increased expression of Lin28b was accompanied by reduced expression of Let7, followed by upregulation of the Let7 targets Myc (190080) and Ras (190020). Rao et al. (2012) concluded that haploinsufficiency of RPL22 can cause T-ALL by activating a pathway that requires NF-kappa-B, LIN28, LET7, and MYC/RAS.
A reciprocal translocation between the long arms of chromosomes 3 and 21, at bands 3q26 and 21q22, occurs as an acquired clonal chromosomal abnormality in malignant cells from patients with therapy-related myelodysplastic syndrome or acute myeloid leukemia, as well as in some patients with chronic myeloid leukemia in blast crisis. Nucifora et al. (1993) showed that the gene on chromosome 21 is AML1 (151385), which is fused to the ETO gene (133435) in 8;21 translocations. Nucifora et al. (1993) isolated a fusion cDNA clone from a t(3;21) library derived from a patient with therapy-related myelodysplastic syndrome; this clone contained sequences from AML1 and from EAP (RPL22), which they localized to chromosome 3q26 from the location of the breakpoint on chromosome 3. The fusion clone contained the DNA-binding 5-prime part of AML1 that is fused to ETO in the t(8;21) and, in addition, at least 1 other exon. The translocation replaced the last 9 codons of AML1 with the last 96 codons of EAP. The fusion does not maintain the correct reading frame of EAP and may not lead to a functional chimeric protein.
Nucifora and Rowley (1995) reviewed the involvement of the AML1 gene in the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. Three loci closely situated to each other on 3q26 are involved in fusions with AML1 in the 3;21 translocations: EVI1 (165215), EAP, and MDS1 (600049). They pointed out that the order of the genes on 3q26 is TEL--EAP--MDS1--EVI1 and provided a diagram (their Figure 5) of the 3q26 region containing these genes and of the various chimeric junctions they had isolated from t(3;21) patients.
Uechi et al. (2001) reported that the RPL22 gene maps to chromosome 1p36.3, not chromosome 3q26. They concluded that the chromosomal breakage on 3q26 reported by Nucifora et al. (1993) and Nucifora and Rowley (1995) occurred in a processed RPL22 pseudogene, directing production of a fusion transcript.
Nucifora, G., Begy, C. R., Erickson, R., Drabkin, H. A., Rowley, J. D. The 3;21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1. Proc. Nat. Acad. Sci. 90: 7784-7788, 1993. [PubMed: 8395054] [Full Text: https://doi.org/10.1073/pnas.90.16.7784]
Nucifora, G., Rowley, J. D. AML1 and the 8;21 and 3;21 translocations in acute and chronic myeloid leukemia. Blood 86: 1-14, 1995. [PubMed: 7795214]
Rao, S., Lee, S.-Y., Gutierrez, A., Perrigoue, J., Thapa, R. J., Tu, Z., Jeffers, J. R., Rhodes, M., Anderson, S., Oravecz, T., Hunger, S. P., Timakhov, R. A., Zhang, R., Balachandran, S., Zambetti, G. P., Testa, J. R., Look, A. T., Wiest, D. L. Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood 120: 3764-3773, 2012. [PubMed: 22976955] [Full Text: https://doi.org/10.1182/blood-2012-03-415349]
Shu-Nu, C., Lin, C.-H., Lin, A. An acidic amino acid cluster regulates the nuclear localization and ribosome assembly of human ribosomal protein L22. FEBS Lett. 484: 22-28, 2000. [PubMed: 11056215] [Full Text: https://doi.org/10.1016/s0014-5793(00)02118-9]
Uechi, T., Tanaka, T., Kenmochi, N. A complete map of the human ribosomal protein genes: assignment of 80 genes to the cytogenetic map and implications for human disorders. Genomics 72: 223-230, 2001. [PubMed: 11401437] [Full Text: https://doi.org/10.1006/geno.2000.6470]