The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

SRA1  -  steroid receptor RNA activator 1

Homo sapiens

Synonyms: PP7684, SRA, SRAP, STRAA1, Steroid receptor RNA activator 1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of SRA1

  • The ratio between non-coding and coding SRA isoforms increased during myogenic differentiation of human satellite cells but not myotonic dystrophy patient satellite cells, in which differentiation capacity is affected [1].
  • We have increased SRA RNA-intron-1 relative level in T5 breast cancer cells, which is paralleled by significant changes in the expression of plasminogen urokinase activator and estrogen receptor beta [2]
  • Herein, we report a significant (Student's t-test, P < 0.003) higher SRA-intron-1 relative expression in breast tumors with higher progesterone receptor contents [2].
  • Using a "minigene" strategy, we also showed that artificial RNAs containing the SRA1 intron-1 sequence are alternatively spliced in breast cancer cell lines [3].Western blot showed that SRA protein was expressed at a higher level in PC-3 than in LNCaP cells, suggesting that SRA may be related to hormone-independent growth of prostate cancer [4].
  • To assess SRA function in vivo, a transgenic-mouse model was generated to enable robust human SRA expression by using the transcriptional activity of the mouse mammary tumor virus long terminal repeat [5].
  • Expression analysis and prognostic significance of the SRA1 gene, in ovarian cancer [6].
  • Given the importance of these processes in atherogenesis, these latter functions may prove to make the SRA a multifunctional player in the atherosclerotic process [7].

High impact information on SRA1

  • SRA is the funding member of the new category of bifunctional RNA [8].
  • We demonstrated that whereas SRA ncRNA was indeed an enhancer of of MyoD activity, SRAP prevented this SRA RNA-dependant co-activation [1].
  • The SRAP inhibitory effect is mediated through the interaction of SRAP with its RNA counterpart via its RRM-like domain interacting with the functional sub-structure of SRA RNA, STR7 [1].
  • Biochemical fractionation shows that SRA exists in distinct ribonucleoprotein complexes, one of which contains the nuclear receptor coactivator steroid receptor coactivator 1 [9].
  • SRA is selective for steroid hormone receptors and mediates transactivation via their amino-terminal activation function [9].
  • We provide functional and mechanistic evidence that SRA acts as an RNA transcript; transfected SRA, unlike other steroid receptor coregulators, functions in the presence of cycloheximide, and SRA mutants containing multiple translational stop signals retain their ability to activate steroid receptor-dependent gene expression [9].
  • SLIRP is recruited to endogenous promoters (pS2 and metallothionein), the latter in a SRA-dependent manner, while NCoR promoter recruitment is dependent on SLIRP [10].
  • We identified SLIRP (SRA stem-loop interacting RNA binding protein) binding to a functional substructure of SRA, STR7 [10].

Chemical compound and disease context of SRA1


Biological context of SRA1

  • SRA is the funding member of the new category of bifunctional RNA [8].
  • This study provides a new model for SRA-mediated regulation of MyoD transcriptional activity in the promotion of normal muscle differentiation, which takes into account the nature of SRA molecules present [1]
  • We propose that alternative splicing of intron-1 is one mechanism used by breast cancer cells to regulate the balance between coding and functional noncoding SRA1 RNAs [3].
  • Using 5'-Rapid Amplification of cDNA Extremities (5'-RACE), we have herein identified several putative transcription initiation sites surrounding the second methionine codon and used to generate coding SRA1 transcripts [3].
  • Furthermore, treatment of cells with combinations of SRA, SRC-1, and TIF2 asODNs reduced ERalpha transcriptional activity to an extent greater than individual asODN treatment alone, suggesting that these coactivators cooperate, in at least an additive fashion, to activate ERalpha-dependent target gene expression [12].
  • We suggest that SRA may act to confer functional specificity upon multiprotein complexes recruited by liganded receptors during transcriptional activation [9].
  • Finally, SRA is unable to rescue the loss of activity of the S(118) ERalpha mutant in response to H-Ras(V12), suggesting that phosphorylation of S(118) by MAPK participates in the ligand-independent effect of SRA on ERalpha [13].

Anatomical context of SRA1


Associations of SRA1 with chemical compounds

  • The SRAP inhibitory effect is mediated through the interaction of SRAP with its RNA counterpart via its RRM-like domain interacting with the functional sub-structure of SRA RNA, STR7 [1].
  • We show that SRA potentiates the estrogen-induced transcriptional activity of both ERalpha and ERbeta [13].
  • The presence of an intact serine residue at position 118 (S(118)) in ERalpha AF-1 is required for coactivation of ERalpha by SRA [13].
  • SLIRP is expressed in normal and tumor tissues, contains an RNA recognition motif (RRM), represses NR transactivation in a SRA- and RRM-dependent manner, augments the effect of Tamoxifen, and modulates association of SRC-1 with SRA [10].
  • SRA enhanced ERalpha activity stimulated by 4-hydroxytamoxifen, but was unable to convert this mixed antiestrogen to an ERbeta agonist [17].
  • Exogenous SRA also enhanced AF-2 activity for both receptors, indicating that SRA effects are not limited to AF-1 [17].

Regulatory relationships of SRA1

  • Here, we showed that three isoforms of human SRA enhanced AR activities [4].

Other interactions of SRA1


Analytical, diagnostic and therapeutic context of SRA1



  1. Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation. Hubé, F., Velasco, G., Rollin, J., Furling, D., Francastel, C. Nucleic. Acids. Res. (2010) [Pubmed]
  2. Increasing the relative expression of endogenous non-coding Steroid Receptor RNA Activator (SRA) in human breast cancer cells using modified oligonucleotides. Cooper, C., Guo, J., Yan, Y., Chooniedass-Kothari, S., Hube, F., Hamedani, M.K., Murphy, L.C., Myal, Y., Leygue, E. Nucleic. Acids. Res. (2009) [Pubmed]
  3. Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA isoforms in breast cancer cell lines. Hube, F., Guo, J., Chooniedass-Kothari, S., Cooper, C., Hamedani, M.K., Dibrov, A.A., Blanchard, A.A., Wang, X., Deng, G., Myal, Y., Leygue, E. DNA Cell Biol. (2006) [Pubmed]
  4. Expression and function of human steroid receptor RNA activator in prostate cancer cells: role of endogenous hSRA protein in androgen receptor-mediated transcription. Kurisu, T., Tanaka, T., Ishii, J., Matsumura, K., Sugimura, K., Nakatani, T., Kawashima, H. Prostate Cancer Prostatic Dis. (2006) [Pubmed]
  5. Steroid receptor RNA activator stimulates proliferation as well as apoptosis in vivo. Lanz, R.B., Chua, S.S., Barron, N., Söder, B.M., DeMayo, F., O'Malley, B.W. Mol. Cell. Biol. (2003) [Pubmed]
  6. Expression analysis and prognostic significance of the SRA1 gene, in ovarian cancer. Leoutsakou, T., Talieri, M., Scorilas, A. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  7. Macrophage scavenger receptor class A: A multifunctional receptor in atherosclerosis. de Winther, M.P., van Dijk, K.W., Havekes, L.M., Hofker, M.H. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  8. When one is better than two: RNA with dual functions. Ulveling, D., Francastel, C., Hubé, F. Biochimie. (2010) [Pubmed]
  9. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Lanz, R.B., McKenna, N.J., Onate, S.A., Albrecht, U., Wong, J., Tsai, S.Y., Tsai, M.J., O'Malley, B.W. Cell (1999) [Pubmed]
  10. SLIRP, a small SRA binding protein, is a nuclear receptor corepressor. Hatchell, E.C., Colley, S.M., Beveridge, D.J., Epis, M.R., Stuart, L.M., Giles, K.M., Redfern, A.D., Miles, L.E., Barker, A., MacDonald, L.M., Arthur, P.G., Lui, J.C., Golding, J.L., McCulloch, R.K., Metcalf, C.B., Wilce, J.A., Wilce, M.C., Lanz, R.B., O'Malley, B.W., Leedman, P.J. Mol. Cell (2006) [Pubmed]
  11. The steroid receptor RNA activator protein is expressed in breast tumor tissues. Chooniedass-Kothari, S., Hamedani, M.K., Troup, S., Hubé, F., Leygue, E. Int. J. Cancer (2006) [Pubmed]
  12. Reduction of coactivator expression by antisense oligodeoxynucleotides inhibits ERalpha transcriptional activity and MCF-7 proliferation. Cavarretta, I.T., Mukopadhyay, R., Lonard, D.M., Cowsert, L.M., Bennett, C.F., O'Malley, B.W., Smith, C.L. Mol. Endocrinol. (2002) [Pubmed]
  13. Ligand-independent coactivation of ERalpha AF-1 by steroid receptor RNA activator (SRA) via MAPK activation. Deblois, G., Giguère, V. J. Steroid Biochem. Mol. Biol. (2003) [Pubmed]
  14. Biological characterization of multidrug-resistant human colon carcinoma sublines induced/selected by two methods. Yang, L.Y., Trujillo, J.M. Cancer Res. (1990) [Pubmed]
  15. Mimicking phosphorylation at Ser-48 strongly reduces surface expression of human macrophage scavenger receptor class A: implications on cell motility. Heider, H., Wintergerst, E.S. FEBS Lett. (2001) [Pubmed]
  16. A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity. Kawashima, H., Takano, H., Sugita, S., Takahara, Y., Sugimura, K., Nakatani, T. Biochem. J. (2003) [Pubmed]
  17. SRA coactivation of estrogen receptor-alpha is phosphorylation-independent, and enhances 4-hydroxytamoxifen agonist activity. Coleman, K.M., Lam, V., Jaber, B.M., Lanz, R.B., Smith, C.L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  18. Altered expression of estrogen receptor coregulators during human breast tumorigenesis. Murphy, L.C., Simon, S.L., Parkes, A., Leygue, E., Dotzlaw, H., Snell, L., Troup, S., Adeyinka, A., Watson, P.H. Cancer Res. (2000) [Pubmed]
  19. Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Lanz, R.B., Razani, B., Goldberg, A.D., O'Malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  20. Pseudo-steroid resistant asthma. Thomas, P.S., Geddes, D.M., Barnes, P.J. Thorax (1999) [Pubmed]
WikiGenes - Universities