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.
Krupp
G
G
Institut für Allgemeine Mikrobiologie, Christian-Albrechts-Universität, Kiel, Germany.
D000818:Animals; D001483:Base Sequence; D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009694:Nucleic Acid Precursors / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D012329:RNA, Bacterial; D016337:RNA, Catalytic / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D043262:Ribonuclease P
D009694:Nucleic Acid Precursors; D016376:Oligonucleotides, Antisense; D012329:RNA, Bacterial; D016337:RNA, Catalytic; D012343:RNA, Transfer; D004722:Endoribonucleases; C468368:RPP14 protein, human; D043262:Ribonuclease P