title: Structural basis for protein-RNA recognition in telomerase.
abstract: Telomerase is a large ribonucleoprotein complex minimally composed of a catalytic telomerase reverse transcriptase (TERT) and an RNA component (TR) that provides the template for telomeric DNA synthesis. However, it remains unclear how TERT and TR assemble into a functional telomerase. Here we report the crystal structure of the conserved regions 4 and 5 (CR4/5) of TR in complex with the TR-binding domain (TRBD) of TERT from the teleost fish Oryzias latipes. The structure shows that CR4/5 adopts an L-shaped three-way-junction conformation with its two arms clamping onto TRBD. Both the sequence and conformation of CR4/5 are required for the interaction. Our structural and mutational analyses suggest that the observed CR4/5-TRBD recognition is common to most eukaryotes, and CR4/5 in vertebrate TR might have a similar role in telomerase regulation as that of stem-loop IV in Tetrahymena TR.
authors.affiliation: 1] National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. [2] Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan, USA. [3] Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, USA.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Brown
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bley
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, USA.
authors.forename: Dustin P
authors.initials: DP
authors.lastname: Rand
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Wu
authors.affiliation: National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Rongguang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, USA.
authors.forename: Julian J-L
authors.identifier: 0000000272532722
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: 1] National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. [2] Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, Michigan, USA. [3] Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009990:Oryzias / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry*; D017385:Sequence Homology; D019098:Telomerase / Q000737:chemistry* / Q000502:physiology*
chemical_list: D012313:RNA; D019098:Telomerase