title: Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene.
abstract: Metal efflux pumps maintain ion homeostasis in the cell. The functions of the transporters are often supported by chaperone proteins, which scavenge the metal ions from the cytoplasm. Although the copper ion transporter CopA has been known in Escherichia coli, no gene for its chaperone had been identified. We show that the CopA chaperone is expressed in E. coli from the same gene that encodes the transporter. Some ribosomes translating copA undergo programmed frameshifting, terminate translation in the -1 frame, and generate the 70 aa-long polypeptide CopA(Z), which helps cells survive toxic copper concentrations. The high efficiency of frameshifting is achieved by the combined stimulatory action of a "slippery" sequence, an mRNA pseudoknot, and the CopA nascent chain. Similar mRNA elements are not only found in the copA genes of other bacteria but are also present in ATP7B, the human homolog of copA, and direct ribosomal frameshifting in vivo.
authors.affiliation: Center for Biomolecular Sciences-m/c 870, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, USA.
authors.forename: Sezen
authors.initials: S
authors.lastname: Meydan
authors.affiliation: Center for Biomolecular Sciences-m/c 870, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, USA.
authors.forename: Dorota
authors.initials: D
authors.lastname: Klepacki
authors.affiliation: Center for Biomolecular Sciences-m/c 870, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, USA.
authors.forename: Subbulakshmi
authors.initials: S
authors.lastname: Karthikeyan
authors.affiliation: Center for Biomolecular Sciences-m/c 870, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, USA.
authors.forename: Tõnu
authors.initials: T
authors.lastname: Margus
authors.affiliation: Proteomics Center of Excellence, Northwestern University, 633 Clark Street, Chicago, IL 60208, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Thomas
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Jones
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Yousuf
authors.initials: Y
authors.lastname: Khan
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Briggs
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Dinman
authors.affiliation: Center for Biomolecular Sciences-m/c 870, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, USA. Electronic address: nvazquez@uic.edu.
authors.forename: Nora
authors.initials: N
authors.lastname: Vázquez-Laslop
authors.affiliation: Center for Biomolecular Sciences-m/c 870, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, USA. Electronic address: shura@uic.edu.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Mankin
mesh_terms: D000251:Adenosine Triphosphatases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins; D018965:Frameshifting, Ribosomal; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D009690:Nucleic Acid Conformation; D010443:Peptide Chain Termination, Translational; D010641:Phenotype; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D014162:Transfection
chemical_list: D027682:Cation Transport Proteins; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D012329:RNA, Bacterial; D012333:RNA, Messenger; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; C000612460:copA protein, E coli
keywords: copA; nascent peptide; pseudoknot; recoding; ribosome profiling; slippery sequence; translation regulation