Non-apoptotic death of the C. elegans linker cell is primed by MYRF-1 activation of pqn-41/polyQ

Yarychkivska, O.; Liu, S.; Horowitz, L. B.; Newland, S.; Wu, P.; Mittal, S.; Tamura, S.; Novosolova, T.; Ritter, D. F.; Lu, Y.; Ercan, S.; Hammell, C.; Shaham, S.

doi:10.64898/2025.12.08.693091

bioRxiv · 10.64898/2025.12.08.693091

Non-apoptotic death of the C. elegans linker cell is primed by MYRF-1 activation of pqn-41/polyQ

Yarychkivska, O.·Liu, S.·Horowitz, L. B.·Newland, S.·Wu, P.·Mittal, S.·Tamura, S.·Novosolova, T.·Ritter, D. F.·Lu, Y.·Ercan, S.·Hammell, C.·Shaham, S.

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Abstract

Linker cell-type death (LCD) is a morphologically conserved non-apoptotic cell-death process with features resembling polyglutamine-dependent neurodegeneration. In C. elegans development, LCD eliminates the male-specific linker cell following its long-range migration. Using single-cell mRNA sequencing of migrating and dying linker cells, we identify myrf-1, encoding a membrane-bound transcription factor implicated in human developmental disorders, as a key LCD regulator. MYRF-1 translocates to the linker cell nucleus during early migration and, surprisingly, its auxin-inducible degradation then, but not later, blocks LCD. MYRF-1 directly binds known LCD genes, including pqn-41, encoding an aggregation-prone polyglutamine protein. Deleting a bona fide MYRF-1-binding site within pqn-41 promotes linker cell survival. Our findings reveal that linker cell death is primed well before cell demise takes place, temporally uncoupling death commitment and execution.

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Yarychkivska, O., Liu, S., Horowitz, L. B., Newland, S., Wu, P., Mittal, S., Tamura, S., Novosolova, T., Ritter, D. F., Lu, Y., Ercan, S., Hammell, C., Shaham, S.. 2025-12-11. Non-apoptotic death of the C. elegans linker cell is primed by MYRF-1 activation of pqn-41/polyQ. https://doi.org/10.64898/2025.12.08.693091

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