F11R expression upon hypoxia is regulated by RNA editing

PLoS One. 2013 Oct 16;8(10):e77702. doi: 10.1371/journal.pone.0077702. eCollection 2013.

Abstract

F11R is a cell adhesion molecule found on the surface of human platelets. It plays a role in platelet aggregation, cell migration and cell proliferation. F11R is subjected to RNA editing, a post-transcriptional modification which affects RNA structure, stability, localization, translation and splicing. RNA editing in the 3'UTR of F11R and RNA levels are increased upon hypoxia. We therefore set to examine if RNA editing plays a role in the increase of F11R RNA seen upon hypoxic conditions. We show that ADAR1, but not ADAR2, takes part in the editing of F11R however editing alone is not sufficient for obtaining an elevation in RNA levels. In addition we show that hyper-edited mature mRNAs are retained in the nucleus and are associated with p54(nrb). We therefore conclude that hypoxia-induced edited RNAs of F11R are preferentially stabilized and accumulate in the nucleus preventing their export to the cytoplasm for translation. This mechanism may be used by additional proteins in the cell as part of the cell's effort to reduce metabolism upon hypoxic stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase
  • Blotting, Western
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Hypoxia / genetics
  • Cell Hypoxia / physiology
  • Cell Line, Tumor
  • Electroporation
  • Humans
  • Immunoprecipitation
  • Male
  • Polymerase Chain Reaction
  • RNA Editing / genetics*
  • RNA, Messenger / genetics
  • RNA-Binding Proteins
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*

Substances

  • Cell Adhesion Molecules
  • F11R protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Receptors, Cell Surface
  • ADARB1 protein, human
  • Adenosine Deaminase

Grant support

Amisragaz is a non-medical and non-pharmaceutical Israeli company that philanthropically supports our Pediatric Intensive Care Department. The current work was funded by general internal departmental resources. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.