We study in particular an RNA-binding domain called ANTAR, which binds a two-hairpin element to prevent transcription termination.
Our laboratory investigates different mechanisms of transcription attenuation in bacteria. In these mechanisms, a transcription termination site is controlled in a signal-dependent manner by a cis-acting regulatory RNA. In particular, we are studying the structure and function of an RNA-binding protein domain called ANTAR. We investigate the determinants for ANTAR-RNA recognition and use this information to predict ANTAR-based regulons.
The transcription elongation protein NusG is present in all cells; we discovered a discrete phylogenetic subfamily called LoaP, which affects transcription elongation of secondary metabolite pathways
Processive antitermination (PA) occurs when RNA polymerase is modified to become resistant to downstream pause and termination sites. There are only a few classes of PA mechanisms that have been discovered. We discovered and are investigating two new classes: (1) an RNA element called ‘EAR’, which alone promotes PA of operons encoding expolysaccharides, and (2) a subclass of NusG proteins called LoaP, which promotes PA of gene clusters encoding secondary metabolites.
Microcompartments house specific cargo enzymes, such as those that are responsible for ethanolamine catabolism
Microcompartments are organelle-like structures, which package specific enzymes inside the microcompartment lumen. They allow exchange of substrates, products and cofactors through surface-associated pores and are assembled and disassembled under specific cellular conditions. We collaborate with Dr. Danielle Garsin’s lab (UT Health Science Center at Houston) to study microcompartments for ethanolamine utilization.
When coupled to fluorescent output platforms, riboswitches can provide single-cell information about metabolite dynamics
Riboswitches are cis-acting, signal-responsive regulatory RNAs. Our laboratory is particularly interested in metal-sensing riboswitches. We investigate: (1) their structural characteristics, (2) the genes that they regulate, and (3) their synthetic applications. For the latter, we are currently exploring how riboswitches can be used for live-cell imaging of metabolite dynamics.
NrmT proteins comprise a discrete, deep-branching outgroup of the Nramp family of proteins. Some or all of NrmT proteins transport magnesium.
As a result of our efforts in studying metal-sensing riboswitches, we discovered a new class of magnesium transport proteins called NrmT. These proteins are evolutionarily related to Nramp transport proteins, which are not traditionally assumed to transport this metal. Furthermore, they are widely used among bacteria. Also, we believe this transporter interacts with additional cytoplasmic proteins that affect its activity. For all of these reasons, we are studying the structure and function of these magnesium transporters.
ome enzymes appear to specialize in the recycling of dinucleotides, which is an activity that affects nucleotide signaling pathways.
There are many types of noncoding RNAs that have been discovered to regulate bacterial gene expression. However, another increasingly large category of RNA-based regulatory factors are signaling nucleotides, including but definitely not limited to cyclic nucleotides (e.g., cAMP), cyclic dinucleotides (e.g., cyclic di-GMP, cyclic di-AMP). In a collaborative project with Drs. Vincent Lee and Holger Sondermann, we are investigating some of the RNase enzymes that affect recycling of these ribonucleotide signals.