Single Molecule Imaging of the Epitranscriptome
RNA molecules play highly diverse functions in living cells, including carrying genetic information (mRNA), performing catalytic functions (e.g. ribozyme and ribosome) and regulating gene expression (e.g. various types of noncoding RNAs). Research in my group has been focused on RNA-mediated gene regulation, including trans-acting small regulatory RNAs (sRNAs( in bacterial systems, and RNA internal modifications in eukaryotic systems.
Bacterial sRNAs are largely stressed-induced, and can directly bind to mRNAs or protein factors to regulate gene expression through diverse mechanisms. Therefore sRNAs are important for firing stress response and providing growth benefit for bacterial cells. Our goal for this research direction is to understand the molecular mechanisms of sRNA-based gene regulation, as well as the impact of this regulation on the interactions between bacterial pathogens and host cells.
Internal RNA modifications are emerging epitranscriptomic markers that provide additional layer for gene regulation, and are linked to development and human diseases. The complex and dynamic nature of RNA modifications make them advantageous, as they can provide timely responses to the signaling cues and fine tune gene expression. Therefore, such modification-based regulation should be gene-specific, signaling-dependent, and quantitative. We aim to decipher the regulatory signals encoded by the modification pattern of RNA at molecular and cellular levels. We are developing imaging platforms for RNA modification detection and quantification inside cells, such that specific methylation state(s) of a single RNA can be mechanistically correlated to a specific regulatory outcome.