Structures and Mechanisms of Nonsegmented, Negative-Strand RNA Virus Polymerases

Abstract

The nonsegmented, negative-strand RNA viruses (nsNSVs), also known as the order Mononegavirales, have a genome consisting of a single strand of negative-sense RNA. Integral to the nsNSV replication cycle is the viral polymerase, which is responsible for transcribing the viral genome, to produce an array of capped and polyadenylated messenger RNAs, and replicating it to produce new genomes. To perform the different steps that are necessary for these processes, the nsNSV polymerases undergo a series of coordinated conformational transitions. While much is still to be learned regarding the intersection of nsNSV polymerase dynamics, structure, and function, recently published polymerase structures, combined with a history of biochemical and molecular biology studies, have provided new insights into how nsNSV polymerases function as dynamic machines. In this review, we consider each of the steps involved in nsNSV transcription and replication and suggest how these relate to solved polymerase structures.