title: RNA BIOCHEMISTRY. Factor-dependent processivity in human eIF4A DEAD-box helicase.
abstract: During eukaryotic translation initiation, the small ribosomal subunit, assisted by initiation factors, locates the messenger RNA start codon by scanning from the 5' cap. This process is powered by the eukaryotic initiation factor 4A (eIF4A), a DEAD-box helicase. eIF4A has been thought to unwind structures formed in the untranslated 5' region via a nonprocessive mechanism. Using a single-molecule assay, we found that eIF4A functions instead as an adenosine triphosphate-dependent processive helicase when complexed with two accessory proteins, eIF4G and eIF4B. Translocation occurred in discrete steps of 11 ± 2 base pairs, irrespective of the accessory factor combination. Our findings support a memory-less stepwise mechanism for translation initiation and suggest that similar factor-dependent processivity may be shared by other members of the DEAD-box helicase family.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Cuauhtémoc
authors.initials: C
authors.lastname: García-García
authors.affiliation: Biophysics Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Frieda
authors.affiliation: Department of Molecular and Cellular Biology, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Kateryna
authors.initials: K
authors.lastname: Feoktistova
authors.affiliation: Department of Molecular and Cellular Biology, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fraser
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA. Department of Applied Physics, Stanford University, Stanford, CA 94305, USA. sblock@stanford.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Block
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D039601:Eukaryotic Initiation Factor-4A / Q000737:chemistry*; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry*; D039642:Eukaryotic Initiation Factors / Q000737:chemistry*; D006801:Humans; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012313:RNA / Q000737:chemistry
chemical_list: C113920:EIF4G1 protein, human; D039603:Eukaryotic Initiation Factor-4G; D039642:Eukaryotic Initiation Factors; C031799:eIF-4B; D012313:RNA; D000255:Adenosine Triphosphate; D004247:DNA; D039601:Eukaryotic Initiation Factor-4A