Inhibition of protein synthesis by 2′–5′ linked adenine oligonucleotides in intact cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1978-11

AUTHORS

BRYAN R. G. WILLIAMS, IAN M. KERR

ABSTRACT

A SERIES of 2–5 linked oligoadenylic acid triphosphate (2–5A) inhibitors of cell-free protein synthesis are formed from ATP by an enzyme (2–5A synthetase) activated in interferon-treated cell extracts or rabbit reticulocyte lysates by double-stranded RNA1–4. The major active species is the trimer, pppA2′p5′A2′p5′A. Cell-free protein synthesis is inhibited by subnanomolar concentrations of 2–5A and this inhibition seems to be mediated at least in part, by a nuclease which degrades mRNA5. However, 2–5A, the nuclease and the inhibition of protein synthesis are all unstable in cell-free systems. 2–5A is rapidly degraded in such systems prepared from control (or interferon-treated) cells, nuclease activity is transient and in the absence of a 2–5A regenerating system protein synthesis resumes if fresh mRNA is added6,7. Extracts derived from cells that have never been treated with interferon, therefore, have mechanisms for the synthesis of 2–5A (rabbit reticulocytes) and for responding to and degrading 2–5A. Thus, the 2–5A system, in addition to any role it has in the antiviral action of interferon, may also be involved in the regulation of normal cell growth and development. The extraordinary potency of 2–5A and its instability in cell-free systems makes the task of detecting 2–5A in intact cells very difficult. As an alternative we have studied the effect of exogenous 2–5A on protein synthesis in intact cells, using a recently described method for making animal cells reversibly permeable to small molecules8. Here we report that pppA2′p5′A2′p5′A and related 2′–5′ linked oligonucleotides inhibit protein synthesis in hypertonically treated BHK–21 cells. More... »

PAGES

88-90

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/276088a0

DOI

http://dx.doi.org/10.1038/276088a0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021304988

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/740027


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