Time-series transcriptome analysis reveals the cascade mechanism of biological processes following the perturbation of the MVA pathway in Salvia miltiorrhiza

Various biological processes are interconnected in plants. Transcription factors (TFs) often act as regulatory hubs to regulate plant growth and responses to stress by integrating various biological pathways. Despite extensive studies on TFs functions in various plant species, our understanding of the details of TFs regulation remains limited. In this study, clonal seedlings of Salvia miltiorrhiza were exposed to specific inhibitors for 12 h. Time-series transcriptome data, sampled hourly, were used to construct co-expression networks and gene regulatory networks (GRNs). Transcriptome dynamic analysis was utilized to capture the gene expression dynamics of various biological processes and decipher the potential molecular mechanisms that regulate these processes. The perturbation results showed the growth and development processes of S.miltiorrhiza were primarily affected at the early stage, whereas stress response-related biological processes were mainly influenced at the later stage. And there was a correlation between the series of key differentially expressed genes in terpenoid biosynthesis pathways and the topological distribution of these pathways. Furthermore, the GRNs based on TFs indicate that TFs play a crucial role in connecting various biological processes. In the cytoplasmic lysate gene regulatory module, SmWRKY48-SmTCP4-SmWRKY28 constituted a regulation hub regulating S.miltiorrhiza responses to perturbation of the MVA pathway. The regulation hub mediated various pathways, including pyruvate metabolism, glycolysis/gluconeogenesis, amino acid metabolism, and ubiquinone and other terpenoid-quinone biosynthesis.Our findings suggest that perturbation of a key biological pathway in S.miltiorrhiza has time-dependent effects on other biological processes. And SmWRKY48-SmTCP4-SmWRKY28 constitutes the regulatory hub in S.miltiorrhiza responses to perturbation of MVA pathway. After disrupting the MVA pathway in Salvia miltiorrhiza with specific inhibitors, a gene regulatory network involving transcription factors reveals a potential mechanism for the synergistic effects of interconnected biological processes.