Alternative titles; symbols
HGNC Approved Gene Symbol: EWSAT1
Cytogenetic location: 15q23 Genomic coordinates (GRCh38): 15:69,080,850-69,095,824 (from NCBI)
Long noncoding RNAs, such as EWSAT1, are predicted to function in gene regulation, predominantly by interacting with chromatin-modifying complexes (Marques Howarth et al., 2014).
Chromosomal translocation that results in EWS (EWSR1; 133450) and FLI1 (193067) gene fusion is pathognomonic for Ewing sarcoma (612219). Using RNA sequencing to identify genes upregulated following expression of an EWS/FLI1 fusion protein in primary pediatric mesenchymal progenitor cells, Marques Howarth et al. (2014) identified EWSAT1. Database analysis revealed 2 additional EWSAT1 splice variants. RNA sequence data suggested that EWSAT1 was predominantly expressed in Ewing sarcoma family tumors, with much lower expression in normal and cancerous breast tissue, and little to no expression in other normal adult or fetal tissues and tumor tissues examined. RT-PCR confirmed expression of EWSAT1 in Ewing sarcoma cell lines and primary patient-derived xenografts compared with non-EWS/FLI1-expressing tissues.
Using short hairpin RNAs, Marques Howarth et al. (2014) found that knockdown of EWSAT1 inhibited proliferation and colony formation in an A673 Ewing sarcoma cell line. Knockdown of EWS/FLI1 or EWSAT1 altered expression of an overlapping set of genes, and EWSAT1 appeared to predominantly repress gene expression. Overexpression of EWSAT1 was poorly tolerated. RNA-protein binding experiments revealed that EWSAT1 bound 22 proteins, including HNRNPK (600712). RNA immunoprecipitation confirmed interaction between EWSAT1 and HNRNPK. RNA sequencing suggested that interaction between EWSAT1 and HNRNPK participated in EWSAT1-dependent gene repression, but not in EWSAT1-associated gene activation.
Marques Howarth et al. (2014) determined that the EWSAT1 gene contains 6 exons and spans approximately 2.2 kb.
Marques Howarth et al. (2014) reported that the EWSAT1 gene maps to chromosome 15q23 between the NOX5 (606572) and GLCE (612134) genes.
Marques Howarth, M., Simpson, D., Ngok, S. P., Nieves, B., Chen, R., Siprashvili, Z., Vaka, D., Breese, M. R., Crompton, B. D., Alexe, G., Hawkins, D. S., Jacobson, D., Brunner, A. L., West, R., Mora, J., Stegmaier, K., Khavari, P., Sweet-Cordero, E. A. Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis. J. Clin. Invest. 124: 5275-5290, 2014. [PubMed: 25401475] [Full Text: https://doi.org/10.1172/JCI72124]