Functions of the 3' and 5' genome RNA regions of members of the genus Flavivirus

Abstract

The positive sense genomes of members of the genus Flavivirus in the family Flaviviridae are ∼ 11 kb in length and have a 5' type I cap but no 3' poly-A. The 3' and 5' terminal regions contain short conserved sequences that are proposed to be repeated remnants of an ancient sequence. However, the functions of most of these conserved sequences have not yet been determined. The terminal regions of the genome also contain multiple conserved RNA structures. Functional data for many of these structures have been obtained. Three sets of complementary 3' and 5' terminal region sequences, some of which are located in conserved RNA structures, interact to form a panhandle structure that is required for initiation of minus strand RNA synthesis with the 5' terminal structure functioning as the promoter. How the switch from the terminal RNA structure base pairing to the long distance RNA-RNA interaction is triggered and regulated is not well understood but evidence suggests involvement of a cell protein binding to three sites on the 3' terminal RNA structures and a cis-acting metastable 3' RNA element in the 3' terminal RNA structure. Cell proteins may also be involved in facilitating exponential replication of nascent genomic RNA within replication vesicles at later times of the infection cycle. Other conserved RNA structures and/or sequences in the 3' and 5' terminal regions have been proposed to regulate genome translation. Additional functions of the 3' and 5' terminal sequences have also been reported.

Keywords: 3′–5′ RNA–RNA interaction; Flavivirus; RNA structures; Viral RNA–cell protein interactions.