Cytidine to Uridine RNA editing: a new model (14241)
Cytidine
(C) to Uridine (U) RNA editing is a post-transcriptional modification that is mediated
by the editosome. The core components of the editosome are reputed to be the deaminase
APOBEC1 and the RNA binding protein A1CF. Apolipoprotein-b
(Apob) mRNA is the most widely
studied example of C to U RNA editing. Editing of Apob mRNA creates a premature stop codon and results in the
production of a smaller APOB protein isoform in the intestine. We have discovered
a novel RNA binding protein, RBM47, that interacts with APOBEC1, A1CF and Apob RNA. RBM47 is expressed in tissues
where C to U RNA editing takes place. It can substitute for A1CF and is
necessary and sufficient for APOBEC1-mediated C to U editing of Apob transcripts in vitro. Editing of Apob
and other potential targets is impaired in Rbm47-deficient
mutant mice. These results point to a functional partnership of RBM47 and APOBEC1
in the basic machinery for C to U RNA editing and call for a revised view of the
composition of the holoenzyme of the editosome. By comparing the transcriptome
of wild type and Rbm47-deficient
mice, we have identified new RNA molecules that are subjected to C to U editing.
Further investigation would reveal the functional attribute of these edited
transcripts.