Poster abstracts

Poster number 6 submitted by Sumirtha Balaratnam

SHARP protein causes the remodeling of SRA1 lncRNA structure

Sumirtha Balaratnam (Kent State University), Joel Caporoso (The University of Akron), Stephanie M. Bilinovich (The University of Akron), Dr. Thomas Leeper (The University of Akron), Dr. Soumitra Basu (Kent State University)

Abstract:
Prostate cancer is one of the two most prevalent forms of cancer in men. The proliferation of prostate cells in the cancer can be directly correlated to transcription of several oncogenes mediated by the nuclear androgen receptor (AR). Androgen receptor stimulation of prostate cancer has been correlated with co-activation from the steroid responsive activator RNA (SRA1). SRA1 is a bifunctional transcript that has recently been found to act not only as a code for protein, but also as a long non-coding RNA (lncRNA). SRA1 has been found to involve in the SRC-1 complex that regulates the transcription of AR. However, the SRA1 assembles in a Ribonucleoprotein (RNP) complex that reduces SRA1 incorporation into SRC-1 complex. SMRT/HDAC1 Associated protein (SHARP) is one protein in the RNP complex that has been previously shown to interact with SRA1 RNA through its four RNA Recognition Motifs (RRMs) and repress the RNA activity. However the specific binding sites of SHARP-RRMs with the SRA1 and their functional roles are still unknown. We investigated the binding of two of the RRM subdomains of SHARP to SRA1 by RNase T1 footprinting. The data show that there was a specific cleavage site at the G52 position of the SRA1-STR7 arm by SHARP-RRM2 which led to the remodeling of the entire SRA1 RNA structure. However, SHARP -RRM1 didn’t show any effect on the SRA1 structure. In addition, the preliminary NMR and Chemical shift perturbation studies indicate that there is a direct interaction between the SHARP and SRA1 RNA. Further studies are required to completely analyze the detailed binding and functional roles of SHARP with SRA1. These studies have potential assist in the development of anti-prostate cancer therapy.

References:
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Keywords: SRA1 lncRNA, SHARP protein, prostate cancer