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

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.