Alternative titles; symbols
HGNC Approved Gene Symbol: SRA1
Cytogenetic location: 5q31.3 Genomic coordinates (GRCh38) : 5:140,550,067-140,558,093 (from NCBI)
Using a yeast 2-hybrid screening system, Lanz et al. (1999) isolated a transcriptional coactivator of steroid nuclear receptors, termed steroid receptor RNA activator (SRA). Northern blot analysis revealed that the SRA gene was expressed in all human tissues tested as major transcripts of approximately 0.7 to 0.85 kb and minor transcripts of approximately 1.3 to 1.5 kb; SRA was expressed at high levels in liver and skeletal muscle and at a low level in brain.
Lanz et al. (1999) found that SRA was selective for steroid hormone receptors and mediated transactivation via their N-terminal activation function. The authors provided functional and mechanistic evidence that SRA acts as an RNA transcript; transfected SRA, unlike other steroid receptor coregulators, functioned in the presence of cycloheximide, and SRA mutants containing multiple translational stop signals retained their ability to activate steroid receptor-dependent gene expression. Biochemical fractionation showed that SRA exists in distinct ribonucleoprotein complexes, one of which contains steroid receptor coactivator-1 (602691). Lanz et al. (1999) suggested that SRA may act to confer functional specificity upon multiprotein complexes recruited by liganded receptors during transcriptional activation.
By immunoprecipitation analysis, Caretti et al. (2006) found that p68 (DDX5; 180630), p72 (DDX17; 608469), and the noncoding RNA SRA associated with MYOD (MYOD1; 159970) in MYOD-transfected HeLa cells. In vitro and in vivo experiments identified p68, p72, and SRA as coactivators of MYOD, and their knockdown in C2C12 mouse myoblast cells prevented proper muscle gene expression and cell differentiation.
By sequence comparisons, Lanz et al. (1999) identified partial SRA sequences isolated as HepG2 3-prime untranslated region (GenBank D16861), EST clones, and chromosome 5 BAC clone 319C17 (GenBank AC005214), providing a preliminary mapping of the SRA gene to chromosome 5.
Caretti, G., Schiltz, R. L., Dilworth, F. J., Di Padova, M., Zhao, P., Ogryzko, V., Fuller-Pace, F. V., Hoffman, E. P., Tapscott, S. J., Sartorelli, V. The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation. Dev. Cell 11: 547-560, 2006. [PubMed: 17011493] [Full Text: https://doi.org/10.1016/j.devcel.2006.08.003]
Lanz, R. B., McKenna, N. J., Onate, S. A., Albrecht, U., Wong, J., Tsai, S. Y., Tsai, M.-J., O'Malley, B. W. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97: 17-27, 1999. [PubMed: 10199399] [Full Text: https://doi.org/10.1016/s0092-8674(00)80711-4]