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

Publikation: Forskning - peer reviewTidsskriftartikel

  • Jesper Buchhave Poulsen
    Jesper Buchhave PoulsenDanmark
  • Kasper Røjkjær Andersen
  • Karina Hansen Kjær
    Karina Hansen KjærDanmark
  • Fiona Durand
    Fiona DurandDepartment of Biochemistry - La Trobe UniversityAustralien
  • Pierre Faou
    Pierre FaouDepartment of Biochemistry - La Trobe UniversityAustralien
  • Anna Lindeløv Vestergaard
  • Gert Hoy Talbo
    Gert Hoy TalboDepartment of Biochemistry - La Trobe UniversityAustralien
  • Nick Hoogenraad
    Nick HoogenraadDepartment of Biochemistry - La Trobe UniversityAustralien
  • Ditlev Egeskov Brodersen
  • Just Justesen
    Just JustesenDanmark
  • 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.
OriginalsprogEngelsk
TidsskriftNucleic Acids Research
Vol/bind39
Tidsskriftsnummer9
Sider (fra-til)3754-70
Antal sider17
ISSN0305-1048
DOI
StatusUdgivet - 2011

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