Alternative titles; symbols
HGNC Approved Gene Symbol: PELO
Cytogenetic location: 5q11.2 Genomic coordinates (GRCh38) : 5:52,787,916-52,804,044 (from NCBI)
Using degenerate primers designed to the Drosophila pelota gene sequence, Shamsadin et al. (2000) cloned a human PELO cDNA from a testis cDNA library. Lai et al. (2000) also identified human PELO, which they called CGI-17, by EST database searching against the C. elegans proteome sequence. The PELO cDNA encodes a 385-amino acid protein with a conserved nuclear localization signal. It shares 70%, 57%, and 36% sequence identity with Drosophila pelota protein, C. elegans R74.6, and yeast DOM34, respectively. By Northern blot analysis, Shamsadin et al. (2000) detected a 1.6-kb PELO transcript in all tissues tested as well as a 2.0-kb testis-specific transcript. By dot blot analysis, Lai et al. (2000) detected PELO expression most abundantly in fetal kidney, spleen, and lung, and in placenta, lung, spleen, kidney, and adrenal gland.
Shamsadin et al. (2000) noted that studies of the Drosophila pelota gene indicate a role in spermatogenesis, mitotic division, and patterning, and that mutations in the related yeast DOM34 gene result in disturbances in the cell cycle and in meiotic cell division.
Guydosh and Green (2014) reported that yeast dom34, orthologous to human PELO, rescues ribosomes that become arrested during translation. Dom34 is also required for separation of free 80S subunits, maturation of ribosomal particles, and rescue of damaged ribosomes. Guydosh and Green (2014) found that yeast dom34 rescued ribosomes that stalled at the 3-prime end of mRNAs that are truncated.
Liakath-Ali et al. (2018) demonstrated that Pelo is required for mammalian epidermal homeostasis. Conditional deletion of Pelo in mouse epidermal stem cells that express Lrig1 (608868) results in hyperproliferation and abnormal differentiation of these cells. By contrast, deletion of Pelo in Lgr5 (606667)-expressing stem cells has no effect and deletion in Lgr6 (606653)-expressing stem cells induces only a mild phenotype. Loss of Pelo results in accumulation of short ribosome footprints and global upregulation of translation, rather than affecting the expression of specific genes. Translational inhibition by rapamycin-mediated downregulation of mTOR rescues the epidermal phenotype. Liakath-Ali et al. (2018) concluded that their study revealed that the ribosome rescue machinery is important for mammalian tissue homeostasis and that it has specific effects on different stem cell populations.
Shamsadin et al. (2000) mapped the PELO gene to 5q11.2 by fluorescence in situ hybridization.
Adham et al. (2003) developed mice deficient in Pelo and found that homozygous deletion was embryonic lethal. Homozygous Pelo null embryos failed to develop past embryonic day 7.5 (E7.5). In culture, mitotic inactive trophoblasts survived, while mitotic active inner cell mass of null blastocysts failed to expand in growth, indicating that the lethality of Pelo null embryos was due to a defect in cell proliferation. Analysis of the cellular DNA content revealed a significant increase of aneuploid cells in Pelo null embryos at E7.5. Adham et al. (2003) hypothesized that an increase in aneuploid cells at E7.5 caused arrested development, suggesting that Pelo is required to maintain genomic stability.
Adham, I. M., Sallam, M. A., Steding, G., Korabiowska, M., Brinck, U., Hoyer-Fender, S., Oh, C., Engel, W. Disruption of the pelota gene causes early embryonic lethality and defects in cell cycle progression. Molec. Cell. Biol. 23: 1470-1476, 2003. [PubMed: 12556505] [Full Text: https://doi.org/10.1128/MCB.23.4.1470-1476.2003]
Guydosh, N. R., Green, R. Dom34 rescues ribosomes in 3-prime untranslated regions. Cell 156: 950-962, 2014. [PubMed: 24581494] [Full Text: https://doi.org/10.1016/j.cell.2014.02.006]
Lai, C.-H., Chou, C.-Y., Ch'ang, L.-Y., Liu, C.-S., Lin, W. Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. Genome Res. 10: 703-713, 2000. [PubMed: 10810093] [Full Text: https://doi.org/10.1101/gr.10.5.703]
Liakath-Ali, K., Mills, E. W., Sequeira, I., Lichtenberger, B. M., Pisco, A. O., Sipila, K. H., Mishra, A., Yoshikawa, H., Wu, C. C.-C., Ly, T., Lamond, A. I., Adham, I. M., Green, R., Watt, F. M. An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis. Nature 556: 376-380, 2018. [PubMed: 29643507] [Full Text: https://doi.org/10.1038/s41586-018-0032-3]
Shamsadin, R., Adham, I. M., von Beust, G., Engel, W. Molecular cloning, expression and chromosome location of the human pelota gene PELO. Cytogenet. Cell Genet. 90: 75-78, 2000. [PubMed: 11060452] [Full Text: https://doi.org/10.1159/000015667]