title: Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code.
abstract: Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering the degenerate genetic code on the ribosome. The number and variety of modifications suggest different mechanisms of action during messenger RNA decoding, of which only a few were described so far. Here, on the basis of several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNA(Lys)(UUU) with hypermodified 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U) at the wobble position discriminates between cognate codons AAA and AAG, and near-cognate stop codon UAA or isoleucine codon AUA, with which it forms pyrimidine-pyrimidine mismatches. We show that mnm(5)s(2)U forms an unusual pair with guanosine at the wobble position that expands general knowledge on the degeneracy of the genetic code and specifies a powerful role of tRNA modifications in translation. Our models consolidate the translational fidelity mechanism proposed previously where the steric complementarity and shape acceptance dominate the decoding mechanism.
authors.affiliation: Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, INSERM, U964; CNRS/University of Strasbourg, UMR7104, 1 rue Laurent Fries, BP 10142, Illkirch 67404, France.
authors.forename: Alexey
authors.initials: A
authors.lastname: Rozov
authors.affiliation: Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, INSERM, U964; CNRS/University of Strasbourg, UMR7104, 1 rue Laurent Fries, BP 10142, Illkirch 67404, France.
authors.forename: Natalia
authors.initials: N
authors.lastname: Demeshkina
authors.affiliation: Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, INSERM, U964; CNRS/University of Strasbourg, UMR7104, 1 rue Laurent Fries, BP 10142, Illkirch 67404, France.|Institute of Fundamental Medicine and Biology, Kazan Federal University, Karl Marx 18, Kazan 420012, Russia.
authors.forename: Iskander
authors.initials: I
authors.lastname: Khusainov
authors.affiliation: Architecture and Reactivity of RNA, Institute of Molecular and Cellular Biology of the CNRS, University of Strasbourg, UPR9002, 15 rue Rene Descartes, Strasbourg 67084, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Westhof
authors.affiliation: Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, INSERM, U964; CNRS/University of Strasbourg, UMR7104, 1 rue Laurent Fries, BP 10142, Illkirch 67404, France.
authors.forename: Marat
authors.initials: M
authors.lastname: Yusupov
authors.affiliation: Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, INSERM, U964; CNRS/University of Strasbourg, UMR7104, 1 rue Laurent Fries, BP 10142, Illkirch 67404, France.
authors.forename: Gulnara
authors.initials: G
authors.lastname: Yusupova
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D003062:Codon / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005815:Genetic Code; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D013891:Thiouridine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D003062:Codon; D012333:RNA, Messenger; D013891:Thiouridine; C011916:5-methylaminomethyl-2-thiouridine; D012343:RNA, Transfer