title: Translational control of recombinant human acetylcholinesterase accumulation in plants.
abstract: BACKGROUND
  Codon usage differences are known to regulate the levels of gene expression in a species-specific manner, with the primary factors often cited to be mRNA processing and accumulation. We have challenged this conclusion by expressing the human acetylcholinesterase coding sequence in transgenic plants in its native GC-rich sequence and compared to a matched sequence with (dicotyledonous) plant-optimized codon usage and a lower GC content.
  
  
  RESULTS
  We demonstrate a 5 to 10 fold increase in accumulation levels of the "synaptic" splice variant of human acetylcholinesterase in Nicotiana benthamiana plants expressing the optimized gene as compared to the native human sequence. Both transient expression assays and stable transformants demonstrated conspicuously increased accumulation levels. Importantly, we find that the increase is not a result of increased levels of acetylcholinesterase mRNA, but rather its facilitated translation, possibly due to the reduced energy required to unfold the sequence-optimized mRNA.
  
  
  CONCLUSIONS
  Our findings demonstrate that codon usage differences may regulate gene expression at different levels and anticipate translational control of acetylcholinesterase gene expression in its native mammalian host as well.
authors.affiliation: The School of Life Sciences and Biodesign Institute, Arizona State University, Tempe, AZ 85287-4501, USA. bgeyer@mainex1.asu.edu <bgeyer@mainex1.asu.edu>
authors.forename: Brian C
authors.initials: BC
authors.lastname: Geyer
authors.forename: Samuel P
authors.initials: SP
authors.lastname: Fletcher
authors.forename: Tagan A
authors.initials: TA
authors.lastname: Griffin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lopker
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
authors.forename: Tsafrir S
authors.initials: TS
authors.lastname: Mor
mesh_terms: D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000235:genetics*; D001482:Base Composition; D003062:Codon / Q000235:genetics; D024861:Genetic Enhancement / Q000379:methods*; D006801:Humans; D030821:Plants, Genetically Modified / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics; D015202:Protein Engineering / Q000379:methods*; D014026:Nicotiana / Q000201:enzymology* / Q000235:genetics*
chemical_list: D003062:Codon; D000110:Acetylcholinesterase