RNA BIOLOGY
RNA orchestrates many integral cellular processes required for cell homeostasis and survival. We are interested in understanding the regulatory roles of RNA within bacterial and eukaryotic systems.
Model summarizing the major steps of E. coli 6S RNA release (bottom) relative to those of transcriptional initiation (top) (adapted from Panchapakesan, 2012)
E.coli 6S RNA regulatory Function
We are interested in studying the E. coli 6S RNA regulatory function. In low nutrient conditions, E. coli are in stationary phase, the 6S is bound to RNA polymerase (RNAP), suppressing sigma70-dependent housekeeping gene expression. Such expression is rapidly resumed in high nutrient conditions as the 6S RNA is released. Dr. Panchapakesan’s initial Scrunching model predicts that 6S RNA release is substantially akin to DNA-dependent mRNA transcription initiation (Panchapakesan, 2012). To further extend this model, I am utilizing an RNA Mango-tagged 6S (Autour et al., 2018) to study the 6S release process in more detail. Success will advance bacteriostatic therapeutic development.
Regulation of immune response by Regnase1 RNase
The essential RNase Regnase1 also known as MCPIP1 and ZC3H12A, plays a key role in regulating a broad range of cellular processes including inflammation and immune response. Regnase1 recognizes specific RNA stem loop secondary structures and upon recognition, degrades target mRNAs. Although a wide range of RNA targets are known, how this substrate recognition mechanism translates into efficient RNA cleavage is not yet well understood. The two main aims of my project are to characterize Regnase1 cleavage motifs using in vitro selection and to understand how common mutations in Regnase1 affect RNA binding and cleavage. This research has the potential to help explain the role of Regnase1 in human cancers (Arthur, 2018).