2013 Rustbelt RNA Meeting
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Poster number 94 submitted by Daniel Morris

Structure and RNA binding studies of Steroid Receptor RNA Activator Protein (SRAp)

Stephanie M. Bilinovich (Chemistry, The University of Akron), Daniel L. Morris (Chemistry, The University of Akron), Thomas C. Leeper (Chemistry, The University of Akron)

Abstract:
Steriod Receptor RNA Activator (SRA) RNA is an RNA with dual roles, acting as both a ncRNA and as a template for a protein (SRAP)1. The protein that the SRA RNA codes for produces a two domain protein with one of the proposed domains acting as an RNA recognition motif due to the presence of the RNA recognition sequence LLVQEL. The second domain is also implicated to serve as a nuclear localization signal2. Previous studies have implicated that the STR7 region of the SRA RNA and SRAP are associated with each other and may be part of the same complex3. SRA RNA and SRAP have been implicated in a wide variety of functions and interactions in vivo. There is particular interest in the role of SRAP in ER+ breast tissue tumors. Studies have shown increased amounts of SRAP within these tumors, however the clinical prognosis of such patients is mixed4,5. Further studies to elucidate the exact mechanism of SRAP’s function are required. Presented here is the structure of the human SRAP of the 2nd domain of the protein via nuclear magnetic resonance (NMR). In addition to the 2nd domain's structure, studies of the full length protein and domain 1 via NMR will be presented. Due to the previous research indicating that the SRA RNA and SRAP are associated with each other, chemical shift perturbation (CPS) with the STR7 region of the RNA will also be discussed.

References:
Chooniedass-Kothari, S., Emberly E., Hamedani, M.K., Troup, S., Wang, X., Czosnek, A.; Hube, F.; Mutawe, M.; Watson, P.H., Leygue, E. FEBS Lett 2004, 566, 43-47

Leygue, E. Nucl Recept Signal 2007 5, e006

Hube, F.; Velasco, G., Rollin J., Furling, D., Francastel C. Nuc Acid Res 2011, 39(2) 513-525

Yan, T., Penner, C.C., Skliris, G.P. , Cooper, C., Nugent, Z., Blanchard, A., Hamedani, M.K., Wang X., Myal, Y., Murphy L.C., Leygue, E. J Cancer Res Clin Oncol 2013, 139(10) 1637-1647

Chooniedass-Kothari, S.; Hamedani, M. K.; Troup S.; Hubé, F.; Leygue, E. Int J Cancer 2006, 118, 1054-1059.

Keywords: SRAP, NMR, cancer