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. CONCLUSION: 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.
