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bioRxiv · 10.64898/2026.01.07.698237

C. elegans E3 ubiquitin ligase EBAX-1 promotes non-apoptotic linker cell-type death through target-directed miRNA degradation

Horowitz, L. B.·Yarychkivska, O.·Lu, Y.·Shaham, S.
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Abstract

Programmed cell death is essential for animal development and homeostasis, and its disruption accompanies many human disorders. Linker cell-type death (LCD) is a morphologically conserved non-apoptotic developmental cell death program with features resembling polyglutamine-dependent neurodegeneration. In C. elegans, LCD execution is mediated by ubiquitin proteasome system (UPS) components, but their proteolytic targets are unknown. Here we demonstrate that EBAX-1/ZSWIM8, a conserved E3 ligase, promotes C. elegans LCD by target directed miRNA degradation (TDMD). We show that EBAX-1 acts cell-autonomously as part of the UPS and requires its Cullin-2 binding motif to promote LCD. Loss of mir-35 family miRNAs, argonautes, or miRNA biogenesis factors, restores LCD to ebax-1 mutants. Furthermore, expression of viln-1/villin mRNA, a predicted mir-35 target, is upregulated in dying cells and is required for LCD. Together, our studies suggest that TDMD mediated by EBAX-1 is important for the fidelity of non-apoptotic developmental cell death.

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Horowitz, L. B., Yarychkivska, O., Lu, Y., Shaham, S.. 2026-01-08. C. elegans E3 ubiquitin ligase EBAX-1 promotes non-apoptotic linker cell-type death through target-directed miRNA degradation. https://doi.org/10.64898/2026.01.07.698237

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