The structural basis of transfer RNA mimicry and conformational plasticity by a viral RNA

Abstract

RNAis arguably themost functionally diverse biologicalmacromolecule. In some cases a single discrete RNA sequence performs multiple roles, and this can be conferred by a complex three-dimensional structure. Suchmultifunctionality can also be driven or enhanced by the ability of a given RNA to assume different conformational (and therefore functional) states1. Despite its biological importance, a detailed structural understanding of the paradigm of RNA structure- driven multifunctionality is lacking. To address this gap it is useful to study examples from single-stranded positive-sense RNA viruses, a prototype being the tRNA-like structure (TLS) found at the 3′ end of the turnip yellow mosaic virus (TYMV). This TLS not only acts like a tRNA to drive aminoacylation of the viral genomic (g)RNA2-4, but also interacts with other structures in the 3′ untranslated region of thegRNA 5, contains the promoter for negative-strand synthesis, and influences several infection-critical processes6. TLS RNA can provide a glimpse into the structural basis of RNA multifunctionality and plasticity, but for decades its high-resolution structure has remained elusive. Here we present the crystal structure of the completeTYMVTLS to 2.0Å resolution. Globally, the RNA adopts a shape that mimics tRNA, but it uses a very different set of intramolecular interactions to achieve this shape. These interactions also allow the TLS to readily switch conformations. In addition, the TLS structure is 'two faced': one face closely mimics tRNA and drives aminoacylation, the other face diverges from tRNA and enables additional functionality. TheTLS is thus structured to performseveral functions and interact with diverse binding partners, and we demonstrate its ability to specifically bind to ribosomes. © 2014 Macmillan Publishers Limited. All rights reserved.