title: Synthetic Polyamines to Regulate mRNA Translation through the Preservative Binding of Eukaryotic Initiation Factor 4E to the Cap Structure.
abstract: Polyion complexes (PICs) of mRNA with synthetic polyamines are receiving increasing attention as mRNA delivery vehicles, and the search for polyamine structure maximizing the translational efficiency of complexed mRNA becomes a critical research topic. Herein, we discovered that fine-tuning of the protonation status of synthetic polyamines can regulate mRNA translation through the preservative binding of eukaryotic initiation factor 4E to m(7)GpppN (cap structure) on the 5' end of mRNA. A series of polyamines with varied numbers of aminoethylene repeats in their side chains were prepared by an aminolysis reaction of poly(β-benzyl-l-aspartate) and paired with mRNA to form PICs. PICs formed from polyamines with higher numbers of aminoethylene repeats preserved the original translational efficiency to naked mRNA, whereas the efficiency significantly dropped by decreasing the number of aminoethylene repeats in the polyamines. Immunoprecipitation assays using anti-eIF4E antibodies revealed that the binding affinity of eIF4E to the cap structure of mRNA in the PIC was sensitive to the number of charged aminoethylene repeats in the polyamine side chain and was strongly correlated with their translational efficiency. These results indicate that the fine-tuning of the polyamine structure plays a critical role in maximizing the translational efficiency of mRNA in the PICs having potential utility as mRNA delivery vehicles.
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Uchida
authors.forename: Keiji
authors.initials: K
authors.lastname: Itaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uchida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Melbourne , Melbourne, Victoria 3010, Australia.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Suma
authors.forename: Kanjiro
authors.initials: K
authors.lastname: Miyata
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University , 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Oba
authors.affiliation: Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology , R1-11, 4529 Nagatsuta, Midori-ku, Yokohama 226-8503, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D011073:Polyamines; D012315:RNA Caps; D012333:RNA, Messenger