Research
Single-molecule studies on riboswitches using optical tweezers
The leader sequences, in certain bacterial mRNAs, contain regulatory elements that can bind specific metabolites to regulate expression of the downstream genes. These regulatory elements, often referred to as riboswitches undergoes local base pairing changes to distant conformational rearrangements upon binding ligands to modulate the protein expression by turning the genes "ON" or "OFF". Emerging studies indicate that riboswitches can display a myriad of architectures in its ligand binding (or aptamer) domain. Furthermore, the binding events can also vary from single-, dual- to complex cooperative ligand-binding events. Similarly, the biology for mechanism of riboswitch action is also varied, however the most prevalent riboswitches function by turning the genes "OFF" either by transcription termination or by sequestering the shine-dalgarno sequences to inhibit ribosome binding. Recent studies indicate that RNA-dependent Rho proteins may also be involved in riboswitch action.
We are using mechanical force to probe the conformational switching in riboswitches in real time. The results from single-molecule studies will provide a detailed understanding of the ligand induced RNA-folding and the associated energy landscapes that are crucial for gene regulatory networks during transcription.