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bioRxiv · 10.64898/2025.12.09.693339

RNA methyltransferase CMTR-1 inhibition activates a GATA transcription factor-mediated protective immune response

Ghosh, A.·Singh, J.
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Abstract

Organisms can activate innate immunity not only by detecting pathogens but also by sensing disturbances to essential cellular processes. Such damage-based surveillance provides a means to identify cellular disruptions that prime host immunity even in the absence of infection. To uncover pathways that enhance immunity, we perform a forward genetic screen in Caenorhabditis elegans for mutants with elevated intestinal immune activation. This screen identifies a hypomorphic allele of the conserved mRNA cap 2-O-methyltransferase cmtr-1, which strongly induces immune effector expression. Transcriptomic profiling reveals the broad activation of innate immune responses, and functional analyses demonstrate that this response requires the GATA transcription factor ELT-2. Notably, loss of cmtr-1 increases resistance to Pseudomonas aeruginosa, indicating that reduced RNA cap methylation can elicit protective immunity. Together, these findings reveal a previously unrecognized mechanism of immune surveillance and demonstrate that perturbation of CMTR-1 serves as a danger signal, triggering an ELT-2-dependent protective immune response.

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Ghosh, A., Singh, J.. 2025-12-12. RNA methyltransferase CMTR-1 inhibition activates a GATA transcription factor-mediated protective immune response. https://doi.org/10.64898/2025.12.09.693339

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