APOBEC-1 is the Cytidine Deaminase Responsible for NF1 and ApoB mRNA Editing
Amedeo J. Cappione and Gary R. Skuse
The neurofibromatosis type 1 gene (NF1) encodes a tumor suppressor which functions through its interaction with the product of the protooncogene ras. An editing site within the NF1 mRNA was identified
by its homology with the apolipoprotein B (apoB) editing site. Early experiments found that overexpression of the cytidine deaminase (APOBEC-1) responsible for apoB editing did not lead to an increase in NF1
editing levels in two cell lines suggesting that either a different enzyme was involved with NF1 editing or that accessory proteins necessary for NF1 mRNA editing were limiting.
The mouse myoblast cell line does not edit its endogenous NF1 mRNA due to divergence from the human sequence yet has the capacity to edit human NF1 expressed from a transfected recombinant vector. Upon
induction of differentiation, these cells exhibit a 4-5 fold increase in the levels of human NF1 mRNA editing. Analyses of APOBEC-1 mRNA levels reveal an approximately 2X increase while editing of endogenous
apoB mRNA does not change.
Overexpression of APOBEC-1 from a recombinant vector does lead to an increase in apoB mRNA editing
levels. Inhibition of APOBEC-1 expression by expression of antisense transcripts from a recombinant vector reduces the levels of both NF1 and apoB editing. Taken together these results suggest that NF1 and
apoB mRNAs are substrates for the same cytidine deaminase, namely APOBEC-1.