Antisense oligoribonucleotides and RNase P. A great potential.

This paper presents the possible--but at present mostly hypothetical--applications of RNase P for the specific inactivation of target RNAs. The natural substrates for RNase P are pre-tRNAs. The enzyme can also recognize and cleave smaller model substrates. These are simple hairpins for bacterial RNase P whereas the requirements for eukaryotic RNase P are more complex and less well understood. It is possible to split the RNase P substrates into two separate RNA molecules. One part of the split substrate RNA contains the RNase P cleavage site and the 5'-terminal half of the acceptor stem, embedded in a large target RNA. The other part of the substrate RNA provides the 3'-terminal half of the acceptor stem and it serves as antisense sequence ('external guide sequence'). Both parts can hybridize and reconstitute a functional substrate for RNase P; this results in cleavage of the target RNA by RNase P. The properties of this system are presented and advantages and problems discussed.