Diversity and modularity of tyrosine-accepting tRNA-like structures

Abstract

Certain positive-sense single-stranded RNA viruses contain elements at their 3′ termini that structurally mimic tRNAs. These tRNA-like structures (TLSs) are classified based on which amino acid is covalently added to the 3′ end by host aminoacyl-tRNA synthetase. Recently, a cryoEM reconstruction of a representative tyrosine-accepting tRNA-like structure (TLS^Tyr) from brome mosaic virus (BMV) revealed a unique mode of recognition of the viral anticodon-mimicking domain by tyrosyl-tRNA synthetase. Some viruses in the hordeivirus genus of Virgaviridae are also selectively aminoacylated with tyrosine, yet these TLS RNAs have a different architecture in the 5′ domain that comprises the atypical anticodon loop mimic. Herein, we present bioinformatic and biochemical data supporting a distinct secondary structure for the 5′ domain of the hordeivirus TLS^Tyr compared to those in Bromoviridae. Despite forming a different secondary structure, the 5′ domain is necessary to achieve robust in vitro aminoacylation. Furthermore, a chimeric RNA containing the 5′ domain from the BMV TLS^Tyr and the 3′ domain from a hordeivirus TLS^Tyr are aminoacylated, illustrating modularity in these structured RNA elements. We propose that the structurally distinct 5′ domain of the hordeivirus TLS^Tyrs performs the same role in mimicking the anticodon loop as its counterpart in the BMV TLS^Tyr. Finally, these structurally and phylogenetically divergent types of TLS^Tyr provide insight into the evolutionary connections between all classes of viral tRNA-like structures.