SRA1 explained

Steroid receptor RNA activator 1 also known as steroid receptor RNA activator protein (SRAP) is a protein that in humans is encoded by the SRA1 gene.^{[1] [2]} The mRNA transcribed from the SRA1 gene is a component of the ribonucleoprotein complex containing NCOA1. This functional RNA also encodes a protein.^[3]

Function

This gene is involved in transcriptional coactivation by steroid receptor. There is currently data suggesting this gene encodes both a non-coding RNA that functions as part of a ribonucleoprotein complex and a protein coding mRNA. Increased expression of both the transcript and the protein is associated with cancer.^[2]

Interactions

SRA1 has been shown to interact with:

• Estrogen receptor alpha,^[4]
• DDX17,^[4]
• Nuclear receptor coactivator 2,^[4] and
• SPEN.^[5]

The SRAP has been shown to interact with its SRA RNA counterpart indirectly with the functional sub-structure STR7 of SRA RNA.^[6] Originally proposed to be RRM containing, SRAP has been demonstrated to have a helix bundle at its C-terminal end while N-terminal to this domain appears unstructured.^[7]

Further reading

• Ulveling D, Francastel C, Hubé F . When one is better than two: RNA with dual functions . Biochimie . 93 . 4 . 633–44 . April 2011 . 21111023 . 10.1016/j.biochi.2010.11.004 . 22165949 .
• Hubé F, Velasco G, Rollin J, Furling D, Francastel C . Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation . Nucleic Acids Research . 39 . 2 . 513–25 . January 2011 . 20855289 . 3025577 . 10.1093/nar/gkq833 .
• Cooper C, Guo J, Yan Y, Chooniedass-Kothari S, Hube F, Hamedani MK, Murphy LC, Myal Y, Leygue E . Increasing the relative expression of endogenous non-coding Steroid Receptor RNA Activator (SRA) in human breast cancer cells using modified oligonucleotides . Nucleic Acids Research . 37 . 13 . 4518–31 . July 2009 . 19483093 . 2715257 . 10.1093/nar/gkp441 .
• Hube F, Guo J, Chooniedass-Kothari S, Cooper C, Hamedani MK, Dibrov AA, Blanchard AA, Wang X, Deng G, Myal Y, Leygue E . 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 . DNA and Cell Biology . 25 . 7 . 418–28 . July 2006 . 16848684 . 10.1089/dna.2006.25.418 . 1807.1/831 . free .
• Leygue E, Dotzlaw H, Watson PH, Murphy LC . Expression of the steroid receptor RNA activator in human breast tumors . Cancer Research . 59 . 17 . 4190–3 . September 1999 . 10485452 .
• Murphy LC, Simon SL, Parkes A, Leygue E, Dotzlaw H, Snell L, Troup S, Adeyinka A, Watson PH . Altered expression of estrogen receptor coregulators during human breast tumorigenesis . Cancer Research . 60 . 22 . 6266–71 . November 2000 . 11103781 .
• Cavarretta IT, Mukopadhyay R, Lonard DM, Cowsert LM, Bennett CF, O'Malley BW, Smith CL . Reduction of coactivator expression by antisense oligodeoxynucleotides inhibits ERalpha transcriptional activity and MCF-7 proliferation . Molecular Endocrinology . 16 . 2 . 253–70 . February 2002 . 10.1210/mend.16.2.0770 . 11818499 . free .
• Kucera T, Waltner-Law M, Scott DK, Prasad R, Granner DK . A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1 . The Journal of Biological Chemistry . 277 . 29 . 26098–102 . July 2002 . 12118039 . 10.1074/jbc.M204013200 . free .
• Ueda T, Mawji NR, Bruchovsky N, Sadar MD . Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells . The Journal of Biological Chemistry . 277 . 41 . 38087–94 . October 2002 . 12163482 . 10.1074/jbc.M203313200 . free .
• Lanz RB, Razani B, Goldberg AD, O'Malley BW . Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA) . Proceedings of the National Academy of Sciences of the United States of America . 99 . 25 . 16081–6 . December 2002 . 12444263 . 138568 . 10.1073/pnas.192571399 . 2002PNAS...9916081L . free .
• Emberley E, Huang GJ, Hamedani MK, Czosnek A, Ali D, Grolla A, Lu B, Watson PH, Murphy LC, Leygue E . Identification of new human coding steroid receptor RNA activator isoforms . Biochemical and Biophysical Research Communications . 301 . 2 . 509–15 . February 2003 . 12565891 . 10.1016/S0006-291X(02)03070-X .
• Watkins RE, Davis-Searles PR, Lambert MH, Redinbo MR . Coactivator binding promotes the specific interaction between ligand and the pregnane X receptor . Journal of Molecular Biology . 331 . 4 . 815–28 . August 2003 . 12909012 . 10.1016/S0022-2836(03)00795-2 .
• Deblois G, Giguère V . Ligand-independent coactivation of ERalpha AF-1 by steroid receptor RNA activator (SRA) via MAPK activation . The Journal of Steroid Biochemistry and Molecular Biology . 85 . 2–5 . 123–31 . June 2003 . 12943696 . 10.1016/S0960-0760(03)00225-5 . 34194523 .
• Lanz RB, Chua SS, Barron N, Söder BM, DeMayo F, O'Malley BW . Steroid receptor RNA activator stimulates proliferation as well as apoptosis in vivo . Molecular and Cellular Biology . 23 . 20 . 7163–76 . October 2003 . 14517287 . 230309 . 10.1128/MCB.23.20.7163-7176.2003 .
• Fleming FJ, Hill AD, McDermott EW, O'Higgins NJ, Young LS . Differential recruitment of coregulator proteins steroid receptor coactivator-1 and silencing mediator for retinoid and thyroid receptors to the estrogen receptor-estrogen response element by beta-estradiol and 4-hydroxytamoxifen in human breast cancer . The Journal of Clinical Endocrinology and Metabolism . 89 . 1 . 375–83 . January 2004 . 14715875 . 10.1210/jc.2003-031048 . free .
• Xu B, Koenig RJ . An RNA-binding domain in the thyroid hormone receptor enhances transcriptional activation . The Journal of Biological Chemistry . 279 . 32 . 33051–6 . August 2004 . 15180993 . 10.1074/jbc.M404930200 . free .
• Zhao X, Patton JR, Davis SL, Florence B, Ames SJ, Spanjaard RA . Regulation of nuclear receptor activity by a pseudouridine synthase through posttranscriptional modification of steroid receptor RNA activator . Molecular Cell . 15 . 4 . 549–58 . August 2004 . 15327771 . 10.1016/j.molcel.2004.06.044 . free .
• Coleman KM, Lam V, Jaber BM, Lanz RB, Smith CL . SRA coactivation of estrogen receptor-alpha is phosphorylation-independent, and enhances 4-hydroxytamoxifen agonist activity . Biochemical and Biophysical Research Communications . 323 . 1 . 332–8 . October 2004 . 15351741 . 10.1016/j.bbrc.2004.08.090 .

Notes and References

1. Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, Tsai MJ, O'Malley BW . Ming-Jer Tsai . A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex . Cell . 97 . 1 . 17–27 . April 1999 . 10199399 . 10.1016/S0092-8674(00)80711-4 . free .
2. Web site: Entrez Gene: SRA1 steroid receptor RNA activator 1.
3. Chooniedass-Kothari S, Emberley E, Hamedani MK, Troup S, Wang X, Czosnek A, Hube F, Mutawe M, Watson PH, Leygue E . The steroid receptor RNA activator is the first functional RNA encoding a protein . FEBS Letters . 566 . 1–3 . 43–7 . May 2004 . 15147866 . 10.1016/j.febslet.2004.03.104 . free .
4. Watanabe M, Yanagisawa J, Kitagawa H, Takeyama K, Ogawa S, Arao Y, Suzawa M, Kobayashi Y, Yano T, Yoshikawa H, Masuhiro Y, Kato S . A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor alpha coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA . The EMBO Journal . 20 . 6 . 1341–52 . March 2001 . 11250900 . 145523 . 10.1093/emboj/20.6.1341 .
5. Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM . Sharp, an inducible cofactor that integrates nuclear receptor repression and activation . Genes & Development . 15 . 9 . 1140–51 . May 2001 . 11331609 . 312688 . 10.1101/gad.871201 .
6. Hubé F, Velasco G, Rollin J, Furling D, Francastel C . Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation . Nucleic Acids Research . 39 . 2 . 513–25 . January 2011 . 20855289 . 3025577 . 10.1093/nar/gkq833 .
7. Bilinovich SM, Davis CM, Morris DL, Ray LA, Prokop JW, Buchan GJ, Leeper TC . The C-terminal domain of SRA1p has a fold more similar to PRP18 than to an RRM and does not directly bind to the SRA1 RNA STR7 region . Journal of Molecular Biology . 426 . 8 . 1753–65 . April 2014 . 24486611 . 10.1016/j.jmb.2014.01.007 .