Andrey S. Krasilnikov

Structural Biology of RNA and RNA-Protein Complexes

At first glance, the destiny of an RNA molecule might appear to be restrained by simplicity of its components and limited to carrying genetic information and helping to decode it. Indeed, RNA molecules are made of only four different types of building blocks and even after addition of common modifications of the bases, the variety does not approach the diversity found in proteins. What can be built of only four different bases? Remarkably, RNA is a very flexible 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 the three-dimensional structure of the molecule 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 MRP, an ubiquitous eukaryotic enzyme that consists of a large RNA component and a number of proteins and is involved in initiation of DNA replication in mitochondria, maturation of 5.8S rRNA and regulation of the cell cycle in yeast. Certain mutations in the RNA component of RNase MRP cause Cartilage-Hair Hypoplasia, a severe autosomal disorder in humans. We are also interested in the putative catalytic core of the spliceosome and some other fascinating and important molecules.

Crystal structures of the specificity domains of the two major types of bacterial Ribonuclease P (RNase P). RNase P is a universal RNA-based enzyme (ribozyme) responsible, among other things, for processing of the 5’- ends of tRNA; specificity domain (S-domain) is an independently folding part of RNase P responsible for substrate recognition and binding. Comparison of the two structures shows that the functionally important core regions are structurally preserved at the local level, while the overall fold of the molecules differs due to variability in auxiliary elements that serve to stabilize this invariant three-dimensional core, involved in substrate recognition.

Representative Publications:

• Perederina A, Esakova O, Koc H, Schmitt ME, Krasilnikov AS (2007). Specific binding of a Pop6/Pop7 heterodimer to the P3 stem of yeast RNase MRP and RNase P RNAs. RNA 13: 1648-1655.
• Baird NJ, Srividya N, Krasilnikov AS, Mondragon A, Sosnick TR, Pan T (2006). Structural basis for altering the stability of homologous RNAs from a mesophilic and a thermophilic bacterium. RNA 12: 598-606.
• Torres-Larios A, Swinger, KK, Krasilnikov AS, Pan T, Mondragon A (2005). Crystal structure of the RNA component of bacterial Ribonuclease P. Nature 437: 584-587.
• Krasilnikov AS, Xiao Y, Pan T, Mondragon A (2004). Basis for structural diversity in homologous RNAs. Science 306: 104-107.
• Krasilnikov AS, Yang XJ, Pan T, Mondragon A (2003). Crystal structure of the specificity domain of ribonuclease P. Nature 421: 760-764.
• Krasilnikov AS, Mondragon A (2003). On the occurrence of the T-loop RNA folding motif in large RNA molecules. RNA 9:640-643.

Search the MEDLINE database at PubMed for articles by A S Krasilnikov