Co-option of an extracellular protease for transcriptional control of nutrient degradation in the fungus Aspergillus nidulans

Li et al. report the PnmB protease as a moonlighting protein in the fungus Aspergillus nidulans as both a secreted protease that degrades extracellular nutrients and an intracellular protease that controls the turnover of the co-repressor NmrA. These results reveal a regulatory mechanism of the drivers of the nitrogen starvation response, as well as the functional evolution of a protease gene for transcriptional regulation and extracellular nutrient breakdown. Nutrient acquisition is essential for all organisms. Fungi regulate their metabolism according to environmental nutrient availability through elaborate transcription regulatory programs. In filamentous fungi, a highly conserved GATA transcription factor AreA and its co-repressor NmrA govern expression of genes involved in extracellular breakdown, uptake, and metabolism of nitrogen nutrients. Here, we show that the Aspergillus nidulans PnmB protease is a moonlighting protein with extracellular and intracellular functions for nitrogen acquisition and metabolism. PnmB serves not only as a secreted protease to degrade extracellular nutrients, but also as an intracellular protease to control the turnover of the co-repressor NmrA, accelerating AreA transcriptional activation upon nitrogen starvation. PnmB expression is controlled by AreA, which activates a positive feedback regulatory loop. Hence, we uncover a regulatory mechanism in the well-established controls determining the response to nitrogen starvation, revealing functional evolution of a protease gene for transcriptional regulation and extracellular nutrient breakdown.

Automated summary

The study revealed the dual functions of the PnmB protein in Aspergillus nidulans as a moonlighting protein, serving both as an extracellular protease for nutrient degradation and an intracellular protease for controlling the turnover of the co-repressor NmrA, accelerating transcriptional activation under nitrogen starvation conditions.