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Microbial transformation of potassium feldspar to produce organic composite potassium fertilizer is recognized to be an important method of effective use of the huge reserves of low grade K+-bearing rock in China. The mechanism underlying microbial weathering of silicate minerals is still unclear, and this is an obstacle to practical methods of application. To thoroughly understand the molecular mechanism responsible for the weathering of potassium feldspar byAspergillus nigerat a molecular level, high-throughput RNA-sequencing (RNA-seq) and treatment with different potassium sources (cultured in Czapek medium with soluble K+or potassium feldspar) were used to investigate the differentially expressed genes ofA.nigerassociated with potassium feldspar weathering and the related metabolic pathways. A series of differentially expressed genes related to the synthesis and transportation of organic acids, polysaccharides, and proteins (enzymes) were found to be closely associated with the K+released from minerals through bioinformatic analysis. In addition, 12 genes that showed apparent expression differences by RNA-seq analysis and are relevant to organic acid synthesis, protein modification, maintenance of cellular homeostasis, and material transportation, were selected to be further verified using RT-qPCR. Compared to the fungal samples cultured with soluble K+, those with potassium feldspar have certain genes that are more up-regulated, such as the genes for Na+,K+-ATPase (447.6 multiples), cystathionine beta-synthase (5.6 multiples), cysteine synthase (9 multiples), and glutathione synthase (3.5 multiples). The analysis indicates thatA. nigerweathering of potassium feldspar is due to the synergistic effect of many factors including the up-regulation of certain genes and activation of related metabolite pathways. The research improves our understanding of the mechanisms of microbial weathering of silicate minerals. [ABSTRACT FROM AUTHOR]