Cordycepin, or 3’-deoxyadenosine, is an adenosine analogue isolated from the Cordyceps genus of parasitic fungi. We show that this anti-cancer drug modifies the sites used for cleavage and polyadenylation in both the budding yeast Saccharomyces cerevisiae and bone marrow-derived macrophages isolated from mice. Despite being known to provoke chain termination during RNA synthesis, cordycepin induced global mRNA 3’ untranslated region (3’ UTR) lengthening. This was accompanied by cellular nucleotide accumulation. Moreover, cordycepin-mediated usage of downstream cleavage and polyadenylation sites in yeast was associated with a permissive chromatin template and was suppressed in the presence of an rpb1 mutation, which slows the RNA polymerase II elongation rate. This suggests that 3' UTR lengthening was a consequence of increased nucleotide availability and faster transcription. In addition, cordycepin addition diminished the inflammatory response induced by LPS in murine macrophages. This included repression of LPS-stimulated Tnf-α and IL-1β expression indicating that cordycepin may also be useful as an anti-inflammatory agent.