Modomics - A Database of RNA Modifications

Published on Jan. 1, 2002 in Am J Hum Genet volume 70(1).

PubMed ID: 11727199

DOI: S0002-9297(07)61281-6


Abstract:

C-->U RNA editing of neurofibromatosis 1 (NF1) mRNA changes an arginine (CGA) to aUGA translational stop codon, predicted to result in translational termination ofthe edited mRNA. Previous studies demonstrated varying degrees of C-->U RNA editingin peripheral nerve-sheath tumor samples (PNSTs) from patients with NF1, but thebasis for this heterogeneity was unexplained. In addition, the role, if any, ofapobec-1, the catalytic deaminase that mediates C-->U editing of mammalianapolipoprotein B (apoB) RNA, was unresolved. We have examined these questions inPNSTs from patients with NF1 and demonstrate that a subset (8/34) manifest C-->Uediting of RNA. Two distinguishing characteristics were found in the PNSTs thatdemonstrated editing of NF1 RNA. First, these tumors express apobec-1 mRNA, thefirst demonstration, in humans, of its expression beyond the luminalgastrointestinal tract. Second, PNSTs with C-->U editing of RNA manifest increasedproportions of an alternatively spliced exon, 23A, downstream of the edited base.C-->U editing of RNA in these PNSTs was observed preferentially in transcriptscontaining exon 23A. These findings were complemented by in vitro studies usingsynthetic RNA templates incubated in the presence of recombinant apobec-1, whichagain confirmed preferential editing of transcripts containing exon 23A. Finally,adenovirus-mediated transfection of HepG2 cells revealed induction of editing ofapoB RNA, along with preferential editing of NF1 transcripts containing exon 23A.Taken together, the data support the hypothesis that C-->U RNA editing of the NF1transcript occurs both in a subset of PNSTs and in an alternatively spliced formcontaining a downstream exon, presumably an optimal configuration for enzymaticdeamination by apobec-1.