Seminars Archive

Expanding the Structural Capabilities of Non-Coding RNA: The Multi-faceted Role of Pseudouridine

Abstract
As a simple polyanion, RNA contains only four different nitrogenous base side chains whose sequence facilitates RNA’s multitude of structural, genetic, and catalytic functions. Our research focuses on understanding the various natural “tools‿ RNA employs to expand its structure/function capabilities within the cell. A vast number of modified bases exist within cellular RNAs beyond the common A, G, C, and U. These bases are introduced into cellular RNAs post-transcriptionally by modifying enzymes that are very often conserved among archea, bacteria, and eukaryotes (Ferré-D’Amaré, 2003). This suggests an ancient role for modified bases in RNA, and evidence for their persistence throughout evolution underscores their importance. Despite widespread modification of RNAs throughout the cell and throughout phylogeny, structural studies of modified RNAs have been limited and attempted explanations regarding their biological purposes speculative. Using biophysical methods such as fluorescence, thermal denaturation monitored by UV absorbance, and NMR spectroscopy, we have characterized the structural and dynamic effects of a post-transcriptionally modified pseudouridine () base that acts to fine-tune and differentiate the function of a spliceosomal RNA. We are currently continuing our investigations on the peptidyl transferase center from human large ribosomal subunit RNA, in which pseudouridines are clustered. References: Ferré-D’Amaré, A. (2003) Curr. Opin. Struc. Biol. 13: 49-55.