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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. Th...

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Detalles Bibliográficos
Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089451/
https://www.ncbi.nlm.nih.gov/pubmed/21245038
http://dx.doi.org/10.1093/nar/gkq1282
Descripción
Sumario: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.