Class of 2006
r.behrouzi@jhu.edu

Research
Many cellular functions are carried out by RNA molecules in connection with or independent of proteins. RNA does not always play as an information carrier, but may act as an enzyme too. And just like a protein, an RNA enzyme can perform its function only if it folds into a particular 3D structure efficiently. But RNA molecules are polyanions and the forces governing their folding transition could be quite different from proteins. For this reason, the structural factors that affect the stability of the native state and the speed and efficiency of reaching it are largely unknown.

I use a large (200 nucleotide) intron located in the Ile tRNA gene of a nitrogen fixing bacterium (Azoarcus sp.) to study these factors. This intron can catalyze its own splicing out of the primary transcript. In vitro, it can also cut substrate oligonucleotides at a specific position. I make several point mutants of this RNA that lack the ability to make certain long distance interactions and then follow the kinetics and thermodynamics of folding transition in them. To do that, I use a range of methods (small angle x-ray scattering (SAXS), various electrophoretic methods, millisecond time resolved hydroxyl radical footprinting and fluorescence) to collect global and local structural information. Finally, I try to put these data together and decipher the factors that affect the folding landscape of large RNA molecules.

Publications