Key regulatory elements that influence the translational fate of mRNA, such as RNA binding proteins, microRNA and m6A methylation, display strong site preference for motifs positioned in the 3’-UTR. In eukaryotes, up to 80% of mRNAs regulate 3’-UTR length by encoding multiple locations for cleavage and polyadenylation (CPA) of the nascent transcript, known as alternative polyadenylation (APA). 3’-deoxyadenosine (3’-dA, also called cordycepin) is a naturally-occurring adenosine analogue known to cause bulk mRNA shortening via chain termination due to its lack of reactive hydroxyl group at the 3’ position. 3’-dA has been used in Chinese medicine for many years for its anti-inflammatory, anti-oxidant and anti-bacterial properties, however its effects on RNA metabolism are poorly understood. Using poly(A)-tail-focused deep sequencing, PAT-seq, we show that, paradoxically, treatment with 3’-dA induces bulk transcript lengthening, favouring distal APA site selection; this phenotype was conserved between yeast and mouse primary bone-marrow-derived macrophages (BMDMs). A PolII slow mutant yeast strain reversed the phenotype, while strains with defective CPA machinery recapitulated it, implicating transcription rate and CPA complex stoichiometry as key determinants of CPA site choice. We also observed signs of mitochondrial dysfunction, and indeed cordycepin-treated BMDMs were unable to respond to LPS challenge, retaining an anti-inflammatory profile due to suppressed interferon-gamma induction. Together our results suggest that the therapeutic effects of 3’-dA lie outside of its established function as an mRNA chain terminator, and this molecule may be applicable to a broader spectrum of inflammatory and transcript-related disorders.