Cytidine to Uridine RNA editing: a new model — University of Technology
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  3. Cytidine to Uridine RNA editing: a new model

Cytidine to Uridine RNA editing: a new model (14241)

Nicolas Fossat 1 2 , Karin Tourle 1 , David Humphreys 3 , Emilie Wilkie 1 , Tania Radziewic 1 , Kristen Barratt 1 , Doreen Liebhold 1 , Joshua B Studdert 1 , Melinda Power 1 , Vanessa Jones 1 , David A F Loebel 1 2 , Jonathan Arthur 1 2 , Thomas Preiss 4 , Patrick P L Tam 1 2
  1. Children's Medical Research Institute, Westmead, NSW, Australia
  2. Sydney Medical School, University of Sydney, Sydney, NSW, Australia
  3. Victor Chang Cardiac Research Institute, Sydney, NSW, Australia
  4. The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
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.
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