Human 2'-phosphodiesterase localizes to the mitochondrial matrix with a putative function in mitochondrial RNA turnover.
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.
Department of Molecular Biology, Aarhus University, C. F. Møllers Allé 3, Denmark.
Jesper Buchhave
JB
Poulsen
Kasper Røjkjær
KR
Andersen
Karina Hansen
KH
Kjær
Fiona
F
Durand
Pierre
P
Faou
Anna Lindeløv
AL
Vestergaard
Gert Hoy
GH
Talbo
Nick
N
Hoogenraad
Ditlev Egeskov
DE
Brodersen
Just
J
Justesen
Pia Møller
PM
Martensen
D000241:Adenosine / Q000032:analysis; D000818:Animals; D002460:Cell Line; D005095:Exoribonucleases / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D021382:Protein Sorting Signals; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000077278:RNA, Mitochondrial; D011994:Recombinant Proteins / Q000032:analysis
D021382:Protein Sorting Signals; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D011994:Recombinant Proteins; D012313:RNA; D005095:Exoribonucleases; C029364:2'-phosphodiesterase; D000241:Adenosine
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