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Peer-reviewedCC BY-NC-NDCellular and molecular life sciences : CMLS

Stella safeguards proteostasis via regulating UBE2D3 translation in the maternal-to-zygotic transition.

  • Guorui Zhang1
  • Minjie Ren1
  • Guangyi Sun2
  • Yilong Zhao1
  • Na Zhang3
  • Qiang Wang4
  • Longsen Han5
5 affiliations
  1. 1State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, 211166, China.
  2. 2Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China.
  3. 3Reproductive Medical Center, Clinical Medical College (Northern Jiangsu People's Hospital), Yangzhou University, Yangzhou, 225001, Jiangsu, China.
  4. 4Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China. [email protected].
  5. 5State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, 211166, China. [email protected].
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Abstract

Ubiquitin-proteasome-mediated protein degradation is essential for maternal-to-zygotic transition, yet the maternal factors that safeguard ubiquitin-proteasome function remain unclear. Here, using a Stella-mutant mouse model, we demonstrate that Stella is required for global protein ubiquitination during early embryogenesis. Stella deficiency in oocytes leads to reduced ubiquitinated protein levels, impaired zygotic genome activation, and early developmental arrest. Proteomic and functional analyses identify UBE2D3 as the key E2 enzyme whose insufficiency underlies the ubiquitination defect. Mechanistically, Stella preserves YBX3 stability, thereby enabling YBX3-dependent translation of Ube2d3 mRNA. Consequently, Stella depletion destabilizes YBX3, diminishes UBE2D3 synthesis, and disrupts protein ubiquitination. Notably, overexpression of Ybx3 or Ube2d3 partially restores ubiquitinated protein levels, zygotic genome activation, and embryo development. These findings identify a previously unrecognized Stella-YBX3-UBE2D3 axis that ensures efficient maternal protein ubiquitination and zygotic genome activation, revealing a cytoplasmic mechanism by which maternal Stella governs proteostasis during maternal-to-zygotic transition.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026stella,
  title = {{Stella safeguards proteostasis via regulating UBE2D3 translation in the maternal-to-zygotic transition.}},
  author = {Guorui Zhang and Minjie Ren and Guangyi Sun and Yilong Zhao and Na Zhang and Qiang Wang and Longsen Han},
  journal = {Cellular and molecular life sciences : CMLS},
  year = {2026},
  month = jul,
  doi = {10.1007/s00018-026-06349-0},
  url = {https://europepmc.org/article/MED/42902058},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Stella safeguards proteostasis via regulating UBE2D3 translation in the maternal-to-zygotic transition.
AU  - Guorui Zhang
AU  - Minjie Ren
AU  - Guangyi Sun
AU  - Yilong Zhao
AU  - Na Zhang
AU  - Qiang Wang
AU  - Longsen Han
PY  - 2026
DA  - 2026/07/01
JO  - Cellular and molecular life sciences : CMLS
DO  - 10.1007/s00018-026-06349-0
UR  - https://europepmc.org/article/MED/42902058
AB  - Ubiquitin-proteasome-mediated protein degradation is essential for maternal-to-zygotic transition, yet the maternal factors that safeguard ubiquitin-proteasome function remain unclear. Here, using a Stella-mutant mouse model, we demonstrate that Stella is required for global protein ubiquitination during early embryogenesis. Stella deficiency in oocytes leads to reduced ubiquitinated protein levels, impaired zygotic genome activation, and early developmental arrest. Proteomic and functional analyses identify UBE2D3 as the key E2 enzyme whose insufficiency underlies the ubiquitination defect. Mechanistically, Stella preserves YBX3 stability, thereby enabling YBX3-dependent translation of Ube2d3 mRNA. Consequently, Stella depletion destabilizes YBX3, diminishes UBE2D3 synthesis, and disrupts protein ubiquitination. Notably, overexpression of Ybx3 or Ube2d3 partially restores ubiquitinated protein levels, zygotic genome activation, and embryo development. These findings identify a previously unrecognized Stella-YBX3-UBE2D3 axis that ensures efficient maternal protein ubiquitination and zygotic genome activation, revealing a cytoplasmic mechanism by which maternal Stella governs proteostasis during maternal-to-zygotic transition.
SN  - 1420-682X
SN  - 1420-9071
ER  -