Natural occurrence of 2',5'-linked heteronucleotides in marine sponges.
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.
Lopp
Annika
A
Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia. annika.lopp@ttu.ee
Reintamm
Tõnu
T
Kuusksalu
Anne
A
Tammiste
Indrek
I
Pihlak
Arno
A
Kelve
Merike
M
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*
D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; D009243:NAD; C023505:2',5'-oligoadenylate; D015088:2',5'-Oligoadenylate Synthetase
J Interferon Res. 1991 Jun;11(3):143-9
1655915
FEBS Lett. 1979 Sep 1;105(1):47-52
226408
Mol Genet Genomics. 2008 Nov;280(5):453-66
18797928
Eur J Biochem. 2002 Mar;269(5):1382-92
11874452
Biomol Eng. 2003 Jul;20(4-6):389-99
12919824
Nucleic Acids Res. 1999 Apr 1;27(7):1609-18
10075991
Nucleic Acids Res. 1980 Jul 25;8(14):3073-85
6160465
Cytokine Growth Factor Rev. 2007 Oct-Dec;18(5-6):351-61
17681872
Dev Comp Immunol. 2007;31(6):539-47
17109960
Analyst. 2009 Aug;134(8):1536-40
20448916
Virology. 1980 Feb;101(1):81-90
6243832
RNA. 2007 Nov;13(11):1834-49
17872511
Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10377-81
1720538
Exp Cell Res. 1998 Mar 15;239(2):379-92
9521856
Pharmacol Ther. 1998 May;78(2):55-113
9623881
Anal Biochem. 1976 May 7;72:248-54
942051
J Biol Chem. 1984 Jan 25;259(2):1363-70
6693390
Biochem Biophys Res Commun. 1981 May 29;100(2):847-56
6268077
Genomics. 2003 Nov;82(5):537-52
14559211
Cancer Res. 1997 Jul 1;57(13):2732-40
9205084
Apoptosis. 2003 Jun;8(3):237-49
12766484
FEBS J. 2007 Jul;274(13):3462-74
17561961
FEBS Lett. 1999 Nov 26;462(1-2):12-8
10580083
Eur J Biochem. 1995 Sep 1;232(2):351-7
7556181
Nucleic Acids Res. 1982 Mar 25;10(6):2163-74
7079179
Integr Comp Biol. 2003 Apr;43(2):281-92
21680435
Eur J Biochem. 1982 Mar 1;122(3):601-8
6277637
J Interferon Res. 1987 Oct;7(5):505-10
2445848
Biochim Biophys Acta. 2002 Jun 12;1590(1-3):140-9
12063177
Proc Natl Acad Sci U S A. 1980 Aug;77(8):4618-22
6933509
Eur J Biochem. 1997 Sep 1;248(2):558-66
9346316
J Mol Evol. 2009 Dec;69(6):612-24
19904482
Trends Biochem Sci. 1995 Sep;20(9):345-7
7482698
Mol Endocrinol. 2000 Feb;14(2):295-306
10674401
Cell Mol Life Sci. 2000 Oct;57(11):1593-612
11092454
J Biol Chem. 2001 Jul 6;276(27):25447-55
11323417
Mol Immunol. 2008 Feb;45(4):945-53
17854897
Virology. 2000 Jan 20;266(2):319-28
10639318
Biochemistry. 2002 Apr 9;41(14):4521-32
11926813
Eur J Biochem. 1998 Oct 15;257(2):420-6
9826188
Cell Mol Life Sci. 2008 Aug;65(16):2613-20
18604630
PLoS Biol. 2007 Apr;5(4):e101
17407382
Cell. 1993 Mar 12;72(5):753-65
7680958