Talk abstracts

Talk on Friday 06:00-07:00pm submitted by Adrian Ferre-DAmare

Structural and sequence-space analysis of natural and artificial catalytic RNAs

Adrian Ferre-DAmare (Howard Hughes Medical Institute, F. Hutchinson Cancer Ctr.)

Abstract:
Catalytic RNAs, or ribozymes, starkly demonstrate the ability of 'naked' RNA to adopt complex three-dimensional architectures that position chemical groups with high precision. Ribozymes play fundamental roles in biological processes such as the homeostatic control of gene expression, genomic replication and protein synthesis. In this lecture, I will discuss studies of catalytic RNAs that emphasize two main experimental approaches. By chemically capturing ribozymes in different functional states and determining their three-dimensional structures we have generated crystallographic 'movies' of these catalysts in action. These studies have produced insights into the molecular basis of ligand and coenzyme recognition and catalysis. We have also employed a combination of in vitro evolution and next generation sequencing to study the fitness landscape of ribozymes. By analyzing the phenotypic fitness of tens of millions of genotypes, these studies reveal the functional importance of each nucleotide, and complement biochemical and structural studies, which are typically restricted to a wild-type sequence and a handful of mutants.

Keywords: Ribozymes, Crystallography, In vitro evolution