TgPRO is an RNA binding protein from T. gondii that binds transcripts that encode proteins with various metabolic functions

ABSTRACT: Organisms ranging from bacteria to tumor cells adjust expression of key metabolic pathways during crowding as they encounter nutrient scarcity, oxidative stress, and waste accumulation. Apicomplexan parasites, including the agents of malaria and toxoplasmosis, similarly encounter crowding within the confined environment of infected cells, yet they lack clear homologs for the regulators of gene expression other species employ during metabolic adaptation. We performed a genome-wide screen in the apicomplexan Toxoplasma gondii to identify genes that support parasite fitness at high multiplicity of infection. The screen revealed increased demand on NAD+ biosynthesis at high density, which is a common feature of crowding, in addition to several parasite-specific factors. Among the previously uncharacterized factors, we found an RNA-binding protein we called T. gondii Parasite Response to Oxidation (TgPRO) for its newfound role regulating the metabolic response to oxidative stress. TgPRO loss elevated levels of reactive oxygen species under ambient conditions, which was rescued by growth at physiological oxygen levels (1%). Loss of TgPRO resulted in smaller chronic cysts—a stage critical for T. gondii transmission—suggesting that redox tension builds with increasing cyst size. We found TgPRO binds specific transcripts, impacting levels of several proteins in carbon metabolism and iron-sulfur cluster assembly. Regulation of the iron-sulfur cluster assembly protein ISCU by TgPRO was dependent on the transcript’s 3′UTR. Through convergent evolution, TgPRO has adopted the role of well-characterized regulators of metabolic adaptation in other organisms, representing the first dedicated regulator of metabolic gene expression in apicomplexan parasites.

ORGANISM(S): Toxoplasma gondii

PROVIDER: GSE327264 | GEO | 2026/09/09

REPOSITORIES: GEO