Cyclases of the 3 '-terminal phosphate in RNA: A new family of RNA processing enzymes conserved in Eucarya, Bacteria and Archaea

The 2',3'-cyclic phosphate termini are produced, as either intermediates or final products, during RNA cleavage by many different endoribonucleases. L ikewise, ribozymes such as hammerheads, hairpins, or the hepatitis delta ri bozyme, generate 2',3'-cyclic phosphate ends. Discovery of the RNA 3'-termi nal phosphate cyclase has indicated that cyclic phosphate termini in RNA ca n also be produced by an entirely different mechanism. The RNA 3'-phosphate cyclase converts the 3'-terminal phosphate in RNA into the 2',3'-cyclic ph osphodiester in the ATP-dependent reaction which involves formation of the covalent cyclase-AMP and the RNA-N-3' pp(5') A intermediates. The findings that several eukaryotic and prokaryotic RNA ligases require the 2',3'-cycli c phosphate for the ligation of RNA molecules raised a possibility that the RNA 3'-phosphate cyclase may have an anabolic function in RNA metabolism b y generating terminal cyclic groups required for Ligation. Recent cloning o f a cDNA encoding the human cyclase indicated that genes encoding cyclase-l ike proteins are conserved among Eucarya, Bacteria, and Archaea. The protei n encoded by the Escherichia coli gene was overexpressed and shown to have the RNA 3'-phosphate cyclase activity. This article reviews properties of t he human and bacterial cyclases, their mechanism of action and substrate sp ecificity. Possible biological functions of the enzymes are also discussed.