Human 2′-phosphodiesterase localizes to the mitochondrial matrix with a putative function in mitochondrial RNA turnover Academic Article uri icon

abstract

  • The vertebrate 2-5A system is part of the innate immune system and central to cellular antiviral defense. Upon activation by viral double-stranded RNA, 5'-triphosphorylated, 2'-5'-linked oligoadenylate polyribonucleotides (2-5As) are synthesized by one of several 2'-5'-oligoadenylate synthetases. These unusual oligonucleotides activate RNase L, an unspecific endoribonuclease that mediates viral and cellular RNA breakdown. Subsequently, the 2-5As are removed by a 2'-phosphodiesterase (2'-PDE), an enzyme that apart from breaking 2'-5' bonds also degrades regular, 3'-5'-linked oligoadenylates. Interestingly, 2'-PDE shares both functionally and structurally characteristics with the CCR4-type exonuclease-endonuclease-phosphatase family of deadenylases. Here we show that 2'-PDE locates to the mitochondrial matrix of human cells, and comprise an active 3'-5' exoribonuclease exhibiting a preference for oligo-adenosine RNA like canonical cytoplasmic deadenylases. Furthermore, we document a marked negative association between 2'-PDE and mitochondrial mRNA levels following siRNA-directed knockdown and plasmid-mediated overexpression, respectively. The results indicate that 2'-PDE, apart from playing a role in the cellular immune system, may also function in mitochondrial RNA turnover.

authors

  • Poulsen, Jesper Buchhave
  • Andersen, Kasper Røjkjær
  • Kjær, Karina Hansen
  • Durand, Fiona
  • Faou, Pierre
  • Vestergaard, Anna Lindeløv
  • Talbo, Gert Hoy
  • Hoogenraad, Nick
  • Brodersen, Ditlev Egeskov
  • Justesen, Just
  • Martensen, Pia Møller

publication date

  • May 2011