title: The structural basis of transfer RNA mimicry and conformational plasticity by a viral RNA.
abstract: RNA is arguably the most functionally diverse biological macromolecule. In some cases a single discrete RNA sequence performs multiple roles, and this can be conferred by a complex three-dimensional structure. Such multifunctionality can also be driven or enhanced by the ability of a given RNA to assume different conformational (and therefore functional) states. 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)RNA, but also interacts with other structures in the 3' untranslated region of the gRNA, contains the promoter for negative-strand synthesis, and influences several infection-critical processes. 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 complete TYMV TLS to 2.0 Å 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. The TLS is thus structured to perform several functions and interact with diverse binding partners, and we demonstrate its ability to specifically bind to ribosomes.
authors.affiliation: 1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [3] Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA (T.M.C.); Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California 92037, USA (J.A.H.).
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Colussi
authors.affiliation: 1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Costantino
authors.affiliation: 1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, USA (T.M.C.); Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California 92037, USA (J.A.H.).
authors.forename: John A
authors.initials: JA
authors.lastname: Hammond
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Ruehle
authors.affiliation: Molecular Biology Consortium, Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Jay C
authors.initials: JC
authors.lastname: Nix
authors.affiliation: 1] Department of Biochemistry and Molecular Genetics, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA [2] Howard Hughes Medical Institute, University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kieft
mesh_terms: D020413:3' Untranslated Regions; D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism; D049148:Aminoacylation; D001483:Base Sequence; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D059370:RNA Folding; D012343:RNA, Transfer / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism; D017806:Tymovirus / Q000235:genetics*; D058727:RNA, Small Untranslated
chemical_list: D020413:3' Untranslated Regions; D012367:RNA, Viral; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases; D058727:RNA, Small Untranslated