Structural studies of RNA and RNA-protein complexes
At first glance, the destiny of an RNA molecule might appear to be restrained by the simplicity of its components - limited to carrying genetic information and helping decode it. Indeed, RNA molecules are made of only four different types of building blocks: even after the addition of common modifications of the bases, the variety does not approach the diversity found in proteins. What can be built with only four different bases? Remarkably, RNA is a very versatile molecule capable of forming intricate networks of various intramolecular interactions. This property allows RNA to fold into complicated three-dimensional structures with features going far beyond simple single strands and double helices. The complexity and diversity of such RNA structures allow RNA to play various advanced roles, including substrate recognition and catalysis. RNA-based enzymes (ribozymes) and complexes of highly structured RNA and proteins play crucial roles in many biological processes including translation, splicing, tRNA and rRNA processing, and so on.
My laboratory is interested in learning the atomic-resolution details of the spatial organization of highly structured RNA molecules and complexes of such molecules with RNA-binding proteins. Using X-ray crystallography we can determine three-dimensional structures of molecules to the finest details; using a combination of crystallographic and biochemical studies we can answer a very broad variety of fundamental questions, ranging from the mechanisms of substrate recognition and catalysis to the structural and functional roles of individual parts of the molecule or complex. Currently we are involved in structural studies of several important RNA molecules and RNA-protein complexes, including Ribonuclease P, Ribonuclease MRP and some other fascinating and important molecules.
Figure: Crystal structure of the P3 domain of yeast RNase MRP in a complex with protein components Pop6 and Pop7.