title: Genome-wide identification and functional analysis of Apobec-1-mediated C-to-U RNA editing in mouse small intestine and liver.
abstract: BACKGROUND
  RNA editing encompasses a post-transcriptional process in which the genomically templated sequence is enzymatically altered and introduces a modified base into the edited transcript. Mammalian C-to-U RNA editing represents a distinct subtype of base modification, whose prototype is intestinal apolipoprotein B mRNA, mediated by the catalytic deaminase Apobec-1. However, the genome-wide identification, tissue-specificity and functional implications of Apobec-1-mediated C-to-U RNA editing remain incompletely explored.
  
  
  RESULTS
  Deep sequencing, data filtering and Sanger-sequence validation of intestinal and hepatic RNA from wild-type and Apobec-1-deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs, all within 3' untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites are unique to liver. Changes in RNA editing lead to corresponding changes in intestinal mRNA and protein levels for 11 genes. Analysis of RNA editing in vivo following tissue-specific Apobec-1 adenoviral or transgenic Apobec-1 overexpression reveals that a subset of targets identified in wild-type mice are restored in Apobec-1-deficient mouse intestine and liver following Apobec-1 rescue. We find distinctive polysome profiles for several RNA editing targets and demonstrate novel exonic editing sites in nuclear preparations from intestine but not hepatic apolipoprotein B RNA. RNA editing is validated using cell-free extracts from wild-type but not Apobec-1-deficient mice, demonstrating that Apobec-1 is required.
  
  
  CONCLUSIONS
  These studies define selective, tissue-specific targets of Apobec-1-dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific.
authors.forename: Valerie
authors.initials: V
authors.lastname: Blanc
authors.forename: Eddie
authors.initials: E
authors.lastname: Park
authors.forename: Sabine
authors.initials: S
authors.lastname: Schaefer
authors.forename: Melanie
authors.initials: M
authors.lastname: Miller
authors.forename: Yiing
authors.initials: Y
authors.lastname: Lin
authors.forename: Susan
authors.initials: S
authors.lastname: Kennedy
authors.forename: Anja M
authors.initials: AM
authors.lastname: Billing
authors.forename: Hisham
authors.initials: H
authors.lastname: Ben Hamidane
authors.forename: Johannes
authors.initials: J
authors.lastname: Graumann
authors.forename: Ali
authors.initials: A
authors.lastname: Mortazavi
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Nadeau
authors.forename: Nicholas O
authors.initials: NO
authors.lastname: Davidson
mesh_terms: D020413:3' Untranslated Regions; D000071479:APOBEC-1 Deaminase; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics*; D003593:Cytoplasm / Q000378:metabolism; D007421:Intestine, Small / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism; D009928:Organ Specificity; D017393:RNA Editing; D034443:RNA Transport; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase