Abstract
Addition of cell extracts prepared from untreated or interferon-treated cells reduced the yield of reovirus RNA synthesized in transcription reactions with purified virions. The reduction observed with the extract of interferon-treated cells was greater than that observed with the extract of untreated cells. The yield of reovirus RNA could be restored to the level obtained without addition of cell extracts by carrying out transcription either in the presence of an inhibitor of 2'-5'-oligoadenylate (2-5A) synthesis, 2'-dATP, or in the presence of the 3'-methyl analog of 5'-monophosphate 2-5A, which inhibits the 2-5A-dependent endoribonuclease. This enzyme was activated in a localized way since neither mRNA added to transcription reactions containing the extract of interferon-treated cells nor rRNA was appreciably degraded, whereas accumulation of reovirus mRNA was drastically inhibited. These findings provide evidence for an antiviral role of the 2-5A synthetase/endoribonuclease system, which preferentially cleaves nascent viral RNA.
MeSH Terms
2',5'-Oligoadenylate Synthetase/metabolism
Endoribonucleases/metabolism
Enzyme Activation
Hydrolysis
Interferons/pharmacology
RNA, Messenger/metabolism
RNA, Viral/metabolism
Reoviridae/growth & development,metabolism
Chemicals
RNA, Messenger
RNA, Viral
Interferons
2',5'-Oligoadenylate Synthetase
Endoribonucleases
2-5A-dependent ribonuclease
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Baglioni C
De Benedetti A
Williams G J
References (26)
26 references, click to expand
-
Radioimmune, radiobinding and HPLC analysis of 2-5A and related oligonucleotides from intact cells.
Nature. 1980 Nov 13;288(5787):189-92
PMID: 6159552
-
Role of 2',5'-oligo(adenylic acid) polymerase in the degradation of ribonucleic acid linked to double-stranded ribonucleic acid by extracts of interferon-treated cells.
Biochemistry. 1980 Nov 25;19(24):5574-9
PMID: 6161640
-
Analogs of (2'-5')oligo(A). Endonuclease activation and inhibition of protein synthesis in intact cells.
J Biol Chem. 1981 Apr 10;256(7):3253-7
PMID: 6259158
-
Ribosomal RNA cleavage, nuclease activation and 2-5A(ppp(A2'p)nA) in interferon-treated cells.
Nucleic Acids Res. 1981 Apr 10;9(7):1571-81
PMID: 6164990
-
Double-stranded RNA causes synthesis of 2',5'-oligo(A) and degradation of messenger RNA in interferon-treated cells.
J Biol Chem. 1981 Aug 10;256(15):7806-11
PMID: 6167569
-
2',5'-Oligo(A)-activated endoribonuclease. Tissue distribution and characterization with a binding assay.
J Biol Chem. 1981 Nov 10;256(21):10751-4
PMID: 7287731
-
5'-O-Monophosphoryladenylyl(2' goes to 5')adenylyl(2' goes to 5')adenosine is an antagonist of the action of 5'-O-triphosphoryladenylyl-(2' goes to 5')adenylyl(2' goes to 5')adenosine and double-stranded RNA.
Proc Natl Acad Sci U S A. 1981 Oct;78(10):5993-7
PMID: 6947212
-
Control of the ppp(a2'p)nA system in HeLa cells. Effects of interferon and virus infection.
Eur J Biochem. 1982 May;124(1):131-8
PMID: 6177533
-
Synthesis of (2'-5')oligoadenylate and activation of an endoribonuclease in interferon-treated HeLa cells infected with reovirus.
J Virol. 1982 Jun;42(3):1039-45
PMID: 6178844
-
Elevated levels of (2'-5')oligoadenylic acid polymerase activity in growth-arrested human lymphoblastoid Namalva cells.
Mol Cell Biol. 1981 Oct;1(10):932-8
PMID: 6180294
-
Biochemistry of interferons and their actions.
Annu Rev Biochem. 1982;51:251-82
PMID: 6180680
-
A unique set of polypeptides is induced by gamma interferon in addition to those induced in common with alpha and beta interferons.
Nature. 1983 Feb 3;301(5899):437-9
PMID: 6218412
-
Inhibition of mRNA binding to ribosomes by localized activation of dsRNA-dependent protein kinase.
Nature. 1984 Sep 6-11;311(5981):79-81
PMID: 6088993
-
Transcription in vitro by reovirus-associated ribonucleic acid-dependent polymerase.
J Virol. 1970 Jul;6(1):1-11
PMID: 5529847
-
Extraordinary effects of specific monovalent cations on activation of reovirus transcriptase by chymotrypsin in vitro.
J Virol. 1973 Feb;11(2):207-17
PMID: 4347424
-
Reovirus mRNA: transcription and translation.
Cell. 1976 Mar;7(3):305-13
PMID: 947543
-
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
Anal Biochem. 1976 May 7;72:248-54
PMID: 942051
-
Interferon action may be mediated by activation of a nuclease by pppA2'p5'A2'p5'A.
Nature. 1978 Jun 22;273(5664):684-7
PMID: 208001
-
Metabolic stability of 2' 5'oligo (A) and activity of 2' 5'oligo (A)-dependent endonuclease in extracts of interferon-treated and control HeLa cells.
Nucleic Acids Res. 1979 Feb;6(2):767-80
PMID: 424314
-
Synthesis of 2'5'-oligo(A) in extracts of interferon-treated HeLa cells.
J Biol Chem. 1979 Jun 25;254(12):5058-64
PMID: 447635
-
Fibroblast interferon induces synthesis of four proteins in human fibroblast cells.
Proc Natl Acad Sci U S A. 1979 Apr;76(4):1824-7
PMID: 287023
-
Interferon-induced enzymatic activities and their role in the antriviral state.
Cell. 1979 Jun;17(2):255-64
PMID: 455463
-
Differential effects of two interferon-induced translational inhibitors on initiation of protein synthesis.
Eur J Biochem. 1979 May 2;96(1):35-41
PMID: 456366
-
Mechanism for discrimination between viral and host mRNA in interferon-treated cells.
Proc Natl Acad Sci U S A. 1979 Jun;76(6):2600-4
PMID: 223150
-
Interferon action: induction of specific proteins in mouse and human cells by homologous interferons.
Proc Natl Acad Sci U S A. 1979 Oct;76(10):4817-21
PMID: 291901
-
Mechanism of pppA(2'p5'A)n2'p5'AOH synthesis in extracts of interferon-treated HeLa cells.
J Biol Chem. 1980 Jun 10;255(11):5031-5
PMID: 6154699