In soybean [ Glycine max ( L.) Merr.], iron deficiency results in interveinal chlorosis and decreased photosynthetic capacity, leading to stunting and yield loss. In this study, gene expression analyses investigated the role of soybean replication protein A ( RPA) subunits during iron stress. Nine RPA homologs were significantly differentially expressed in response to iron stress in the near isogenic lines ( NILs) Clark (iron efficient) and Isoclark (iron inefficient). RPA homologs exhibited opposing expression patterns in the two NILs, with RPA expression significantly repressed during iron deficiency in Clark but induced in Isoclark. We used virus induced gene silencing ( VIGS) to repress GmRPA3 expression in the iron inefficient line Isoclark and mirror expression in Clark. GmRPA3-silenced plants had improved IDC symptoms and chlorophyll content under iron deficient conditions and also displayed stunted growth regardless of iron availability. RNA- Seq comparing gene expression between GmRPA3-silenced and empty vector plants revealed massive transcriptional reprogramming with differential expression of genes associated with defense, immunity, aging, death, protein modification, protein synthesis, photosynthesis and iron uptake and transport genes. Our findings suggest the iron efficient genotype Clark is able to induce energy controlling pathways, possibly regulated by SnRK1/ TOR, to promote nutrient recycling and stress responses in iron deficient conditions.