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Copper sulfate (CuSO4) is widely used in controlling the Microcystis aeruginosa blooms.Many studies reported the toxicity mechanisms of Cu2+ to M.aeruginosa at the physiological level,but little is known about a transcriptomic basis of these mechanisms.In the present study,M.aeruginosa was treated by 0.5 mg/L Cu2+ (half of the 96-h EC50) for 72 h.The results show that CH2+ content in M.aeruginosa increased after 72 h Cu2+ exposure,whereas the Fv/Fm chlorophyll fluorescence value and chlorophyll a content in M.aeruginosa sharply decreased.Reactive oxygen species concentration and activity of antioxidant enzymes (superoxide dismutase,catalase and peroxidase) were all increased.These physiological data confirmed toxicity of Cu2+ to m.aeruginosa.The RNA-seq analysis showed that 6 646 725 and 7 880 291 clean reads were obtained for the Cu-treated and control libraries,respectively.The 595 genes (252 downward trend and 343 upward trend) with the Gene Ontology (GO) annotations were divided into three main functional categories:cellular component,molecular function,and biological process.In the Cluster of Orthologous Groups (COG) annotation,418 differentially expressed genes with 25 functional definitions were obtained.Among them,‘replication,recombination and repair’,‘energy production and conversion’,and ‘general function prediction only’ were the largest three groups of transcripts.In the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,genes involved in photosynthesis and oxidative phosphorylation were present at the highest percentages.In addition,the genes involved in photosynthesis and oxidative phosphorylation were identified,and then confirmed using real-time PCR.This study reported the first transcriptome of M.aeruginosa.Photosynthesis and oxidative phosphorylation were severely affected by Cu2+ toxicity,which may have contributed to cell death.These data provide the potential mechanism to explain the CuSO4 effect on the harmful M.aeruginosa.