Origin of the interferon-inducible (2′-5′)oligoadenylate synthetases: cloning of the (2′-5′)oligoadenylate synthetase from the marine sponge Geodia cydonium

Abstract

In vertebrates cytokines mediate innate (natural) immunity and protect them against viral infections. The cytokine interferon causes the induction of the (2′-5′)oligoadenylate synthetase [(2-5)A synthetase], whose product, (2′-5′)oligoadenylate, activates the endoribonuclease L which in turn degrades (viral) RNA. Three isoforms of (2-5)A synthetases exist, form I (40–46 kDa), form II (69 kDa), and form III (100 kDa). Until now (2-5)A synthetases have only been cloned from birds and mammals. Here we describe the cloning of the first putative invertebrate (2-5)A synthetase from the marine sponge Geodia cydonium. The deduced amino acid sequence shows signatures characteristic for (2-5)A synthetases of form I. Phylogenetic analysis of the putative sponge (2-5)A synthetase indicates that it diverged first from a common ancestor of the hitherto known members of (vertebrate) (2-5)A synthetases I, (2-5)A synthetases II and III. Moreover, it is suggested that the (2-5)A synthetases II and III evolved from this common ancestor (very likely) by gene duplication. Together with earlier results on the existence of the (2′-5′)oligoadenylates in G. cydonium, the data presented here demonstrate that also invertebrates, here sponges, are provided with the (2-5)A system. At present, it is assumed that this system might be involved in growth control, including control of apoptosis, and acquired its additional function in innate immune response in evolutionarily younger animals, in vertebrates.