C -> U editing of neurofibromatosis 1 mRNA occurs in tumors that express both the type II transcript and apobec-1, the catalytic subunit of the apolipoprotein B mRNA-editing enzyme

C-->U RNA editing of neurofibromatosis 1 (NF1) mRNA changes an arginine (CG A) to a UGA translational stop codon, predicted to result in translational termination of the edited mRNA. Previous studies demonstrated varying degre es of C-->U RNA editing in peripheral nerve-sheath tumor samples (PNSTs) fr om patients with NF1, but the basis for this heterogeneity was unexplained. In addition, the role, if any, of apobec-1, the catalytic deaminase that m ediates C-->U editing of mammalian apolipoprotein B (apoB) RNA, was unresol ved. We have examined these questions in PNSTs from patients with NF1 and d emonstrate that a subset (8/34) manifest C-->U editing of RNA. Two distingu ishing characteristics were found in the PNSTs that demonstrated editing of NF1 RNA. First, these tumors express apobec-1 mRNA, the first demonstratio n, in humans, of its expression beyond the luminal gastrointestinal tract. Second, PNSTs with C-->U editing of RNA manifest increased proportions of a n alternatively spliced exon, 23A, downstream of the edited base. C-->U edi ting of RNA in these PNSTs was observed preferentially in transcripts conta ining exon 23A. These findings were complemented by in vitro studies using synthetic RNA templates incubated in the presence of recombinant apobec-1, which again confirmed preferential editing of transcripts containing exon 2 3A. Finally, adenovirus-mediated transfection of HepG2 cells revealed induc tion of editing of apoB RNA, along with preferential editing of NF1 transcr ipts containing exon 23A. Taken together, the data support the hypothesis t hat C-->U RNA editing of the NF1 transcript occurs both in a subset of PNST s and in an alternatively spliced form containing a downstream exon, presum ably an optimal configuration for enzymatic deamination by apobec-1.