title: 3D RNA and Functional Interactions from Evolutionary Couplings.
abstract: Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces the research on the structure and functional interactions of these RNA gene sequences. We mine the evolutionary sequence record to derive precise information about the function and structure of RNAs and RNA-protein complexes. As in protein structure prediction, we use maximum entropy global probability models of sequence co-variation to infer evolutionarily constrained nucleotide-nucleotide interactions within RNA molecules and nucleotide-amino acid interactions in RNA-protein complexes. The predicted contacts allow all-atom blinded 3D structure prediction at good accuracy for several known RNA structures and RNA-protein complexes. For unknown structures, we predict contacts in 160 non-coding RNA families. Beyond 3D structure prediction, evolutionary couplings help identify important functional interactions-e.g., at switch points in riboswitches and at a complex nucleation site in HIV. Aided by increasing sequence accumulation, evolutionary coupling analysis can accelerate the discovery of functional interactions and 3D structures involving RNA.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Caleb
authors.initials: C
authors.lastname: Weinreb
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Program in Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Riesselman
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Ingraham
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Institute of Pathology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Gross
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: debbie@hms.harvard.edu.
authors.forename: Debora S
authors.initials: DS
authors.lastname: Marks
mesh_terms: D019277:Entropy; D019143:Evolution, Molecular; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D059370:RNA Folding; D022661:RNA, Untranslated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism
chemical_list: D022661:RNA, Untranslated; D016601:RNA-Binding Proteins