The structure-function relationship of the enterovirus 3'-UTR

Abstract

Essential processes in living cells are carried out by large complex assemblies, which typically consist of a large number of proteins and frequently also contain nucleic acids, mostly RNA [Alberts, B., 1998. The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell 92, 291-294]. These large biomolecular complexes carry out biological processes in highly sophisticated ways: molecules do not move around randomly in the cell and interact by chance, but are guided to these "macromolecular machines", in which the number of possible collisions is restricted to a few possibilities, based, e.g., on the specificity of protein-RNA recognition. While the coding capacity of RNA lies within its sequence, the shape of an RNA molecule determines other functionalities such as stability, intra- and intermolecular interactions, catalytic activity, regulation of cellular processes, etc. [Doudna, J.A., 2000. Structural genomics of RNA. Nat. Struct. Biol. 7, 954-956; Cech, T.R. 2000. Structural biology. The ribosome is a ribozyme. Science 289, 878-879]. RNA structures in macromolecular machines are important features in assembly, target recognition and activity. Viral RNA molecules contain cis- and/or trans-acting control elements that, as exemplified by internal ribosomal entry sites and origins of genome replication, consist of complex multidomain structures [Andino, R., Rieckhof, G.E., Achacoso, P.L., Baltimore D., 1993. Poliovirus RNA synthesis utilizes an RNP complex formed around the 5'-end of viral RNA. EMBO J. 12, 3587-3598; Melchers, W.J.G., Hoenderop, J.G.J., Bruins Slot, H.J., Pleij, C.W.A., Pilipenko, E.V., Agol, V.I., Galama, J.M.D., 1997. Kissing of the two predominant hairpin loops in the coxsackie B virus 3' untranslated region is the essential structural feature of the origin of replication required for negative-strand RNA synthesis. J. Virol. 71, 686-696]. The formation of these structures is involved in the specific recognition of ligands or serves to support the structural integrity of the whole element. The replication of the enterovirus RNA is carried out by a large biomolecular complex formed by cis-acting RNA elements found in the 5'- and 3'-UTR of the virus genome and several cellular and viral proteins. This review will focus on RNA elements in the 3'-UTR of enteroviruses.