1. Integrated Techniques for the Study of Ribonucleoprotein Complexes
- Author
-
Caporoso, Joel A., Caporoso
- Subjects
- Chemistry, Biochemistry, SHARP, SRA, NMR, RNP, SAXS, PRE
- Abstract
SMRT/HDAC1 Associated Repressor Protein (SHARP) is a human, multi-domain protein that is involved in multiple transcriptional regulatory pathways. Four RNA Recognition Motifs (RRMs), found near the N-terminus of the protein, are believed to mediate its epigenetic action. SHARP interacts and regulates the activity of the Steroid Receptor Activator RNA (SRA) via these RRMs. Steroid Receptor Activator RNA (SRA) is a long, noncoding RNA (lncRNA) transcript that typically does not participate in translation to make protein, but instead regulates 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 represses the activity of SRA RNA through direct complex formation mediated by its RRMs. The goal of this work is to elucidate RNA-protein interactions that are pivotal to understanding epigenetic regulation by nuclear steroid receptors. To do this, traditional and advanced NMR techniques combined with SAXS, CD, and molecular biology were employed to extensively probe the molecular interactions.
- Published
- 2016