Year: 2003
Type: dissertation
Abstract: RNA assumes many roles in nature. As a structural entity, it is responsible for \nproxying genetic information, ferrying amino acids and organizing ribosome \narchitecture. RNA also participates in several genetic regulatory mechanisms. \nCatalytic RNAs are responsible for the faithful modification of unprocessed \ntransfer, ribosomal and messeger RNAs, and the assembly of proteins from amino \nacid monomers may be performed by RNA-derived catalytic residues in the \nribosome. \nPreviously researchers have developed methods for the isolation of unnatural \nRNA ligands and enzymes from random sequence pools. We have used these \ntechniques in order to develop novel biosensors and biosensor components. RNA \nligands (aptamers) were isolated from a random sequence pool that bind and \ninhibit ricin A-chain, a ribosome-inactivating protein and proposed biological \nwarfare agent. In addition, ribozymes that were previously engineered to respond \nto a set of ligands were incorporated into a sensor platform for the first \ndemonstration of an RNA-based detection system for the simultaneous detection \nof diverse analyte classes including DNA, proteins, peptides and small-molecules. \nWe have also developed a set of computational tools in order to identify \nfunctional RNAs from both random sequence pools and genomic sequence \ndatabases. A computationally-accessible model was conceived in order to \ndescribe and predict the structural rearrangements undergone by allosteric \nribozymes upon ligand binding, and the model was in turn used to select novel \nallosteric ribozymes from random sequence pools. In addition, we have used a \nstructure-based search strategy in order to characterize well-folded regions in \nmRNAs with the goal of discovering additional examples of a novel class of \ngenetic regulatory element, the riboswitches.
Author: Jay R. Hesselberth
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2108906014