Integrative Transcriptomic and Metabolomic Analysis Provides New Insights into the Multifunctional ARGONAUTE 1 Through an Arabidopsis ago1-38 Mutant with Pleiotropic Growth Defects

ARGONAUTE 1 (AGO1) selectively recruits microRNAs (miRNAs) and some small interfering RNAs (siRNAs) to form an RNA-induced silencing complex (RISC) to regulate gene expressions and also promotes the transcription of certain genes through direct chromatin binding. Complete dysfunction of AGO1 causes extremely serious growth arrest and sterility in Arabidopsis. Here, we characterize an <i>ago1-38</i> allele with distinctive morphological abnormalities obviously distinguishing it from the other <i>ago1</i> alleles, such as <i>ago1-25</i> and <i>ago1-45</i>. The aberrant phenotypes of <i>ago1-38</i> were completely restored in its transgenic complementation lines harboring an AGO1 promoter and coding sequence. To investigate the mechanism underlying the unique phenotype of <i>ago1-38</i>, integrated transcriptomic and metabolomic analysis was employed. The glutathione metabolism pathway was significantly co-enriched in the integrated analysis of <i>ago1-38</i>, suggesting an altered balance of the glutathione-related redox system. Transcriptomic analysis showed that many genes in the siRNA processing pathway were significantly changed in <i>ago1-38</i>, suggesting the dysregulation of the siRNA pathway. Meanwhile, numerous genes, particularly the large set of transcriptional factors associated with plant-pathogen interaction networks and phytohormone signaling cascades, exhibited altered expression patterns, implying perturbed immune defense and hormonal signaling. Collectively, these findings provide new insights into the multifaceted roles of AGO1 in siRNA processing, pathogen response, and phytohormone signaling.