Background <p>MicroRNA 398 (miR398), one of the conserved miRNAs, is known to target multiple genes encoding Cu²⁺-containing proteins such as the conserved two Cu/Zn Superoxide dismutases (CSD1 and CSD2) and a Cu²⁺-chaperone for CSDs (CCS) as primary targets. Additionally, miR398 is known to target transcripts of Cu²⁺-containing proteins such as cytochrome C-oxidase, Cupredoxin, and blue copper binding protein (BCBP) that are poorly conserved among plants.</p> Results <p>Our recently generated rice degradomes have validated Selenium Binding Protein (SBP), yet another Cu²⁺-containing protein, as a genuine target of miR398. Because SBP was largely underappreciated target of miR398, we sought to uncover potential conservation of miR398-SBP regulatory module in plants. This analysis revealed that miR398 is targeting <i>SBP</i> transcripts in several monocot clades. Though this regulation was also obvious but less prominent in dicots. Publicly available degradome analysis provided evidence for miR398-induced cleavage on <i>SBP</i> mRNAs in six monocots and four dicots.</p> Conclusions <p>These findings suggest that miR398 has picked up <i>SBP</i> as a secondary target in&#xa0;several clades of monocots, but less frequently in dicots. At the biochemical level, SBP proteins, like CSDs, are Cu²⁺-containing proteins that are thought to function in oxidative stress responses. Thus, miR398 regulates diverse families of Cu²⁺-containing proteins (CSDs and SBPs) that are part of the same biochemical pathway.</p>