title: Natural occurrence of 2',5'-linked heteronucleotides in marine sponges.
abstract: 2',5'-oligoadenylate synthetases (OAS) as a component of mammalian interferon-induced antiviral enzymatic system catalyze the oligomerization of cellular ATP into 2',5'-linked oligoadenylates (2-5A). Though vertebrate OASs have been characterized as 2'-nucleotidyl transferases under in vitro conditions, the natural occurrence of 2',5'-oligonucleotides other than 2-5A has never been demonstrated. Here we have demonstrated that OASs from the marine sponges Thenea muricata and Chondrilla nucula are able to catalyze in vivo synthesis of 2-5A as well as the synthesis of a series 2',5'-linked heteronucleotides which accompanied high levels of 2',5'-diadenylates. In dephosphorylated perchloric acid extracts of the sponges, these heteronucleotides were identified as A2'p5'G, A2' p5'U, A2'p5'C, G2'p5'A and G2' p5'U. The natural occurrence of 2'-adenylated NAD(+) was also detected. In vitro assays demonstrated that besides ATP, GTP was a good substrate for the sponge OAS, especially for OAS from C. nucula. Pyrimidine nucleotides UTP and CTP were also used as substrates for oligomerization, giving 2',5'-linked homo-oligomers. These data refer to the substrate specificity of sponge OASs that is remarkably different from that of vertebrate OASs. Further studies of OASs from sponges may help to elucidate evolutionary and functional aspects of OASs as proteins of the nucleotidyltransferase family.
authors.affiliation: Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia. annika.lopp@ttu.ee
authors.forename: Annika
authors.initials: A
authors.lastname: Lopp
authors.forename: Tõnu
authors.initials: T
authors.lastname: Reintamm
authors.forename: Anne
authors.initials: A
authors.lastname: Kuusksalu
authors.forename: Indrek
authors.initials: I
authors.lastname: Tammiste
authors.forename: Arno
authors.initials: A
authors.lastname: Pihlak
authors.forename: Merike
authors.initials: M
authors.lastname: Kelve
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000227:Adenine Nucleotides / Q000032:analysis*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D009243:NAD / Q000032:analysis; D009843:Oligoribonucleotides / Q000032:analysis*; D011161:Porifera / Q000737:chemistry*
chemical_list: D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; D009243:NAD; C023505:2',5'-oligoadenylate; D015088:2',5'-Oligoadenylate Synthetase
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