title: Heterogeneous cationic liposomes modified with 3β-{N-[(N',N'-dimethylamino)ethyl]carbamoyl}cholesterol can induce partial conformational changes in messenger RNA and regulate translation in an Escherichia coli cell-free translation system.
abstract: The effect of cationic liposomes (CLs) on messenger RNA(mRNA) conformation and translation was studied, focusing on membrane heterogeneity. CLs, composed of 1,2-dioleoyl-sn-glycerol-3-phosphocholine/1,2-dioleoyl-3-timethylammonium propane (DOPC/DOTAP) and DOPC/3β-{N-[(N',N'-dimethylamino)ethyl]carbamoyl}cholesterol (DOPC/DC-Ch), inhibited mRNA translation in an  Escherichia coli  cell-free translation system. Analysis of the membrane fluidity and polarity indicated a heterogeneous DOPC/DC-Ch (70/30) membrane, while other CLs exhibited homogeneous disordered membranes. mRNA adsorbed onto DOPC/DC-Ch liposomes showed translational activity, while DOPC/DOTAP liposomes inhibited mRNA translation in proportion to its adsorption onto membranes. Dehydration of DOPC/DOTAP (70/30) and DOPC/DC-Ch (70/30) was observed in the presence of mRNA but not in the case of zwitterionic DOPC liposomes, indicating that mRNA binds in regions between the phosphate [-PO(2)(-)-] and carbonyl [-C=O-] moieties of lipids. UV resonance Raman spectroscopy suggests that adenine, cytosine, and guanine interact with DOPC/DOTAP (70/30) and DOPC/DC-Ch (70/30) but not with DOPC. Circular dichroism indicates that DOPC/DOTAP (70/30) extensively denatured the mRNA. In contrast, heterogeneous DOPC/DC-Ch (70/30) induced partial conformational changes but maintained the translational activity of mRNA.
authors: Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama-cho, Toyonaka, Osaka 560-8531, Japan.
authors: Keishi
authors: K
authors: Suga
authors: Tomoyuki
authors: T
authors: Tanabe
authors: Hiroshi
authors: H
authors: Umakoshi
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000737:chemistry; D055598:Chemical Phenomena; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry; D004161:Diphenylhexatriene / Q000737:chemistry; D004926:Escherichia coli / Q000166:cytology* / Q000235:genetics*; D057927:Hydrophobic and Hydrophilic Interactions; D007848:Laurates / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009711:Nucleotides / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D007848:Laurates; D008081:Liposomes; D009711:Nucleotides; D012333:RNA, Messenger; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D004161:Diphenylhexatriene; D002784:Cholesterol; D015081:2-Naphthylamine; C065580:laurdan