Biology subjects

Yarychkivska, O.

Publications and source records attributed to Yarychkivska, O..

3 recordsLinked to original sources

bioRxiv2026

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

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.

developmental biology↗

bioRxiv2025

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

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.

cell biology↗

bioRxiv2025

CED-3 caspase promotes dismantling but not onset of non-apoptotic linker cell death in C. elegans

Nuclear degradation accompanies cell death. To study this process, we followed nuclear dismantling of the C. elegans linker cell, which undergoes non-apoptotic morphologically-conserved cell death characterized by nuclear envelope crenellations and cell splitting. We show that although linker cell death is cell autonomous, nucleus elimination follows engulfment and is blocked in rab-35 and arf-6 phagosome maturation mutants. Surprisingly, although linker cell death is independent of the apoptotic caspase CED-3, CED-3 is partially required within the linker cell, and upstream of RAB-35 and ARF-6, for cell splitting, engulfment, and nucleus elimination. In parallel studies, we found that the kinase inhibitor staurosporine causes mouse embryonic fibroblasts to undergo caspase-independent non-apoptotic death accompanied by nuclear crenellations and, paradoxically, by Caspase-3/7 activation. Our findings suggest mechanistic similarities between staurosporine-induced and linker cell death, revealing that, in some contexts, caspases do not initiate cell death but instead promote subcellular tasks required for cell clearance.

cell biology↗