Human 2'-phosphodiesterase localizes to the mitochondrial matrix with a putative function in mitochondrial RNA turnover

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  • Jesper Buchhave Poulsen, Denmark
  • Kasper Røjkjær Andersen
  • Karina Hansen Kjær, Denmark
  • Fiona Durand, Department of Biochemistry - La Trobe University, Australia
  • Pierre Faou, Department of Biochemistry - La Trobe University, Australia
  • Anna Lindeløv Vestergaard, Denmark
  • Gert Hoy Talbo, Department of Biochemistry - La Trobe University, Australia
  • Nick Hoogenraad, Department of Biochemistry - La Trobe University, Australia
  • Ditlev Egeskov Brodersen
  • Just Justesen, Denmark
  • Pia Møller Martensen
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.
Original languageEnglish
JournalNucleic Acids Research
Pages (from-to)3754-70
Number of pages17
Publication statusPublished - 2011

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