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PMID: 6158049 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of the stability of poly(I)xpoly(C)-induced human fibroblast interferon mRNA: selective inactivation of interferon mRNA and lack of involvement of 2',5'-oligo(A) synthetase activation during the shutoff of interferon production.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 77 ·No. 6 ·1980-06-00 ·Pages 3489-93

Sehgal PB, Gupta SL

Abstract

The inactivation of interferon mRNA during the shutoff phase of interferon production in poly(I)xpoly(C)-induced human fibroblast cultures is selective. We have determined that the shutoff of interferon production, which takes place from 3 to 8 hr after the beginning of induction, is not associated with an appreciable declined in the rate of bulk cellular protein synthesis or of cellular protein secretion. While the amount of translatable interferon mRNA declined markedly during the shutoff phase, the level of translatable bulk cellular mRNA and the stability of [3H]uridine-labeled mRNA were unaffected. Superinduction with actinomycin D selectively stabilized interferon mRNA with no apparent effect on the stability of bulk cellular mRNA. Furthermore, an activation of the 2',5'-oligo(A) synthetase/endonuclease system does not appear to be involved in the shutoff phenomenon. Uninduced FS-4 cells contained a low basal level of 2'5'-oligo(A) synthetase activity, which was unchanged in poly(I)xpoly(C)-induced cells during the shutoff phase. Treatment of FS-4 cells with interferon for 16-18 hr prior to induction increased the enzyme activity by approximately 200-fold. However, this did not inhibit interferon production after induction with poly(I)xpoly(C) alone or after superinduction with cycloheximide or actinomycin D or both. Furthermore, the rates of decay of interferon production were comparable in cells with either a basal or an increased level of 2',5'-oligo(A) synthetase. Thus a 200-fold increase in 2',5'-oligo(A) synthetase level did not affect either the stability of interferon mRNA or the efficacy of interferon superinduction by metabolic inhibitors.

MeSH Terms
2',5'-Oligoadenylate Synthetase Adenine Nucleotides/metabolism Animals Cells, Cultured Dactinomycin/pharmacology Female Fibroblasts/metabolism Humans Interferons/biosynthesis,genetics Oligoribonucleotides/metabolism Oocytes Poly I-C/pharmacology Polynucleotide Ligases/metabolism Proteins/metabolism RNA, Messenger/biosynthesis,metabolism Substrate Specificity Time Factors Xenopus/cytology
Chemicals
Adenine Nucleotides Oligoribonucleotides Proteins RNA, Messenger Dactinomycin Interferons 2',5'-Oligoadenylate Synthetase Polynucleotide Ligases Poly I-C
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sehgal P B
Gupta S L
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32 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.77.6.3489
Published
1980-06-00
Pages
3489-93
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC349642
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.77.6.3489 PMC Full Text View journal details
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