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The apolipoprotein B mRNA editing complex performs a multifunctional cycle and suppresses nonsense‐mediated decay

Ann Chester, Angelika Somasekaram, Maria Tzimina, Adam Jarmuz, Jane Gisbourne, Raymond O'Keefe, James Scott, Naveenan Navaratnam

Author Affiliations

  1. Ann Chester1,
  2. Angelika Somasekaram1,
  3. Maria Tzimina1,
  4. Adam Jarmuz1,
  5. Jane Gisbourne1,
  6. Raymond O'Keefe2,
  7. James Scott*,1,3 and
  8. Naveenan Navaratnam*,1
  1. 1 RNA Editing Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK
  2. 2 School of Biological Sciences, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
  3. 3 Imperial College Genetics and Genomics Research Institute, Imperial College, South Kensington Campus, Armstrong Road, London, SW7 2AZ, UK
  1. *Corresponding authors. E-mail: j.scott{at}ic.ac.uk or E-mail: naveenan.navaratnam{at}csc.mrc.ac.uk
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Abstract

The C to U editing of apolipoprotein B (apoB) mRNA is mediated by a minimal complex composed of an RNA‐binding cytidine deaminase (APOBEC1) and a complementing specificity factor (ACF). This editing generates a premature termination codon and a truncated open reading frame. We demonstrate that the APOBEC1—ACF holoenzyme mediates a multifunctional cycle. The atypical APOBEC1 nuclear localization signal is involved in RNA binding and is used to import ACF into the nucleus as cargo. APOBEC1 alone induces nonsense‐mediated decay (NMD). The APOBEC1—ACF complex edits and remains associated with the edited RNA to protect it from NMD. The APOBEC1 nuclear export signal is involved in the export of ACF and the edited apoB mRNA together, to the site of translation.

  • Received March 3, 2003.
  • Revision received May 28, 2003.
  • Accepted June 2, 2003.
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