Description:
<jats:p>The exact physiological function of Ap<jats:sub>3</jats:sub>A (A5′ppp5″A, 5′5″ diadenosine triphosphate) remains unclear. Previously we have demonstrated that the human p46 2‐5A synthetase (OAS1) efficiently utilises Ap<jats:sub>3</jats:sub>A as an acceptor substrate for oligoadenylate synthesis. Here we show that Ap<jats:sub>3</jats:sub>A(2′p5′A)<jats:sub>
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</jats:sub> oligonucleotides can activate the 2‐5A‐dependent RNase (RNase L), when the number of 2′,5′‐linked adenyl residues is two or more. Under the experimental conditions applied the half‐maximal activation (AC<jats:sub>50</jats:sub>) of RNase L for 2′‐adenylated Ap<jats:sub>3</jats:sub>A derivatives was determined to be in nanomolar range while the AC<jats:sub>50</jats:sub> for 2‐5A<jats:sub>3</jats:sub> was 0.4 nM. The Ap<jats:sub>3</jats:sub>A(2′p5′A)<jats:sub>
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</jats:sub> oligonucleotides are thus less effective in activating RNase L than 2‐5A. We also investigated the occurrence of 2′‐adenylated Ap<jats:sub>3</jats:sub>A in interferon and poly(I)·poly(C)‐treated HeLa cells. In purified trichloroacetic acid‐soluble extracts about 40% of RNase L‐activating material is resistant to phosphatase treatment, whereas the removal of 5′‐terminal phosphates greatly reduces the activating properties of 2‐5A. We assume that this activity at least partly may be associated with the presence of 2′‐adenylated Ap<jats:sub>
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</jats:sub>A derivatives with blocked 5′‐terminal phosphates.</jats:p>