The strength of the miR398-Csd2-CCS1 regulon is subject to natural variation in Arabidopsis thaliana.

miR398 links expression of the three major chloroplast copper proteins, plastocyanin, CCS1 and Csd2, to copper availability. miR398 abundance was stronger plastocyanin-controlled in accessions from cold and continental habitats (Kas-1, Ms-0, WS) than in Cvi-0 and Col-0. Target gene regulation was broken for Csd2 in Cvi-0 upon cold-treatment. Comparison of miR398 levels, target gene regulation as well as Ago1 and miR168 expression demonstrated that the miR398 regulon can be overwritten by accession specific transcriptional regulation in Cvi-0. It is concluded that the escape from the miRNA control of copper homeostasis is linked to adaptation of Cvi-0 to its harsh natural habitat.