HMA proteins produce 2',3'-cNMP signaling molecules and activate CNL-mediated immunity in rice

Gong, X.; Niu, G.; Sun, S.; Yan, B.; Li, Z.; Tang, W.; Hu, P.; Zheng, H.; Chen, M.; Ponceler, N.; Xu, Z.; Lv, X.; Lin, H.; Liu, J.; Gao, Y.; Zhu, L.; Wang, X.; Wang, G.-L.; Tharreau, D.; Kang, H.; Deng, Y.; Wang, Z.; Zhang, Y.; He, Z.

doi:10.64898/2026.03.15.711844

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bioRxiv · 10.64898/2026.03.15.711844

HMA proteins produce 2',3'-cNMP signaling molecules and activate CNL-mediated immunity in rice

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Abstract

Plants deploy a sensor repertoire, usually NLRs, to perceive pathogen effectors and activate executor NLR-triggered immunity. Here we reveal that rice HMA proteins function as sensors detecting the Magnaporthe oryzae MAX effector AvrPigm to trigger broad-spectrum blast resistance mediated by the CNL PigmR. AvrPigm is conserved with multiple copies in blast genomes and targets HMA proteins, facilitating HMA translocation into the cytoplasm. Cryo-EM structure of the HPP04HMA reveals a filament-like oligomer with ssDNA/RNA bound inside the filament, which display cyclic nucleotide synthase activity to generate 2',3'-cNMP in a CNL-dependent manner. We further discovered that the LRR domains of the executor CNLs perceive 2',3'-cNMP to mount immunity. Our study thus establishes an unrecognized immunity mode with a distinct repertoire of sensor receptors that produce signaling molecules that are perceived by the LRR domains of executor NLRs to mediate immunity, shedding new light on the sensor-executor conception and immune activation in plants. HighlightsO_LIHMA proteins and CNL receptors form a new sensor-executor mode in plant immunity C_LIO_LICryo-EM reveals the filament-like structure of HMA-ssRNA/ssDNA C_LIO_LIHMA proteins are cyclic nucleotide synthetases to generate 2',3'-cNMP C_LIO_LILRR domains of CNLs perceive 2',3'-cNMP to mediate immunity C_LI

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Gong, X., Niu, G., Sun, S., Yan, B., Li, Z., Tang, W., Hu, P., Zheng, H., Chen, M., Ponceler, N., Xu, Z., Lv, X., Lin, H., Liu, J., Gao, Y., Zhu, L., Wang, X., Wang, G.-L., Tharreau, D., Kang, H., Deng, Y., Wang, Z., Zhang, Y., He, Z.. 2026-03-16. HMA proteins produce 2',3'-cNMP signaling molecules and activate CNL-mediated immunity in rice. https://doi.org/10.64898/2026.03.15.711844

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