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.