Poster abstracts
Poster number 16 submitted by Joel Caporoso
Structure determination and RNA-binding properties of SHARP
Joel A. Caporoso (Department of Chemistry and Biochemistry, The University of Akron), Stephanie M. Bilinovich (Department of Chemistry and Biochemistry, The University of Akron), Thomas C. Leeper (Department of Chemistry and Biochemistry, The University of Akron)
Abstract:
SMRT/HDAC1 Associated Repressor Protein (SHARP) is a multi-domain protein that is involved in multiple transcription regulatory pathways. Of particular interest are the four RNA Recognition Motifs (RRMs) that are found near the N-terminus of the protein. Previous data has suggested that SHARP is involved in interacting and regulating the action of the Steroid Receptor Activator RNA (SRA) through the use of these RRMs. Steroid Receptor Activator RNA (SRA) is a RNA transcript that has recently been found to act not only as code for protein biosynthesis, but also as a long, non-coding RNA (lncRNA). lncRNAs do not participate in translation to make protein, but instead regulate gene expression by interacting with RNA-binding proteins, becoming coactivators for transcription factors, and repressing promoters. SRA, in particular, has been proposed to be involved in multiple complexes that regulate the transcription of nuclear steroid receptors. SHARP, with its four RNA recognition motifs (RRMs), has been shown to interact and form complexes with SRA RNA that are capable of repressing the RNA's activity. Chemical shift perturbation studies via 15N heteronuclear single quantum correlation (HSQC) of SHARP and SRA RNA will be presented and indicate that there is a direct interaction between the two species. A preliminary nuclear magnetic resonance (NMR) structural model of a SHARP RRM with the likely binding pocket for the RNA will be discussed. This structure and other biophysical data on the SRA STR7 arm indicate that SHARP RRM 2 may be involved in RNA structure remodeling.
Keywords: NMR, SHARP, SRA