Arabidopsis Myo-Inositol-1-Phosphate Synthases Moonlight in Nuclear Gene Regulation

Myo-inositol-1-phosphate synthase (MIPS) catalyzes the first committed step of de novo inositol biosynthesis, yet genetic evidence suggests that Arabidopsis MIPS proteins also have catalysis-independent functions. Although moonlighting proteins are increasingly recognized, their identification and functional dissection in plants remain limited. We asked whether the catalytic outputs of MIPS can be uncoupled from its inositol-independent functions. Here, using an inositol-rescue transcriptomic strategy, we separated catalytic inositol-biosynthetic outputs from inositol-independent functions of MIPS in Arabidopsis seedlings. Exogenous inositol had little effect on the wild type but extensively reprogrammed the mips1 mips3 transcriptome without fully restoring it to the wild type state. The inositol-independent branch was associated mainly with nuclear gene-regulatory processes, with broader implications for development and immunity. By contrast, the catalytic branch was linked primarily to cellular metabolism and structural organization, with broader roles in stress responses and polar growth. These findings support a dual-function model in which Arabidopsis MIPS proteins couple cytosolic inositol biosynthesis with candidate moonlighting functions associated with nuclear gene-regulatory modules. More broadly, this work provides a framework for understanding how metabolic enzymes coordinate development and stress responses, and opens new avenues for exploring how plant gene duplication may foster functional innovation and adaptation to environmental change.