Location: Produce Safety and Microbiology ResearchTitle: TOR coordinates nucleotide availability with ribosome biogenesis in plants
|BUSCHE, MICHAEL - University Of California|
|SCARPIN, REGINA - University Of California|
|BRUNKARD, JACOB - University Of California|
Submitted to: The Plant Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/29/2021
Publication Date: 2/4/2021
Citation: Busche, M., Scarpin, R.M., Hnasko, R.M., Brunkard, J.O. 2021. TOR coordinates nucleotide availability with ribosome biogenesis in plants. The Plant Cell. 33(5):1615-1632. https://doi.org/10.1093/plcell/koab043.
Interpretive Summary: We identified critical enzymes and pathways essential for the coordinated regulation of cellular metabolism in plants. When nutrients are abundant these enzymes are active and promote anabolic growth. When nutrients are scares these enzymes are inactive and maintain quiescence via catabolic pathways. We show that plant TOR (Target Of Rapamycin) protein kinase activity is sensitive to nucleotide availability, similar to that of mammalian TOR, and is involved in the maintenance of nucleotide homeostasis in plant cells.
Technical Abstract: TARGET OF RAPAMYCIN (TOR) is a conserved eukaryotic Ser/Thr protein kinase that coordinates growth and metabolism with nutrient availability. We conducted a medium-throughput functional genetic screen to discover essential genes that promote TOR activity in plants, and identified a critical regulatory enzyme, cytosolic phosphoribosyl pyrophosphate (PRPP) synthetase (PRS4). PRS4 synthesizes cytosolic PRPP, a key upstream metabolite in nucleotide synthesis and salvage pathways. We found that prs4 knockouts are embryo-lethal in Arabidopsis thaliana, and that silencing PRS4 expression in Nicotiana benthamiana causes pleiotropic developmental phenotypes, including dwarfism, aberrant leaf shape, and delayed flowering. Transcriptomic analysis revealed that ribosome biogenesis is among the most strongly repressed processes in prs4 knockdowns. Building on these results, we discovered that TOR activity is inhibited by chemical or genetic disruption of nucleotide biosynthesis, but that this effect can be reversed by supplying plants with nucleobases. Finally, we show that TOR transcriptionally promotes nucleotide biosynthesis to support the demands of ribosomal RNA synthesis. We propose that TOR coordinates ribosome biogenesis with nucleotide availability in plants to maintain metabolic homeostasis and support growth.