Chemically modified RNA: approaches and applications

The modification of phosphate into phosphorothioate internucleotidic linkages in various RNAs and their usefulness in identifying phosphate positions essential for function are described. Several modifications of the 2'-hydroxyl group of the ribose, particularly the replacement by fluorine atoms and amino groups, is discussed. These studies have been concentrated on hammerhead ribozymes in order to determine hydroxyl groups important for the catalytic activity. In addition these derivatives have been instrumental in rendering ribozymes more stable toward nucleases.