RNF220 safeguards meiotic synapsis and male fertility by antagonizing SYCE1 ubiquitination.
7 affiliations
- 1State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China.
- 2Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, 650223, China.
- 3State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China. [email protected].
- 4National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China. [email protected].
- 5Department of reproduction and genetics, the First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China. [email protected].
- 6State Key Laboratory of Genetic Evolution and Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China. [email protected].
- 7National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China. [email protected].
Abstract
A homozygous mutation in RNF220, encoding a RING-type E3 ubiquitin ligase, is associated with male infertility featuring small-headed sperm, but the precise roles and mechanisms of RNF220 in spermatogenesis remain elusive. Here, we explored the function of RNF220 in spermatogenesis using a Stra8-Cre-mediated germ cell-specific conditional knockout mouse model. RNF220 was highly expressed in mouse spermatocytes, and its germ cell-specific deletion caused male subfertility, accompanied by testicular atrophy, oligozoospermia, and abnormal sperm morphology. Spermatocyte nuclear spreading assay revealed severe defects in homologous chromosome synapsis and DNA damage repair, as well as elevated apoptosis in pachytene spermatocytes. Mechanistically, SYCE1, a core component of the synaptonemal complex central element essential for synapsis, was identified as a testicular target of RNF220. Notably, RNF220 stabilized SYCE1 by antagonizing its ubiquitination mediated by other ubiquitin ligases. RNF220 deficiency led to reduced SYCE1 protein level and marked increase in its K48-linked polyubiquitination. Furthermore, RNF220-mediated SYCE1 stabilization was independent of its intrinsic ubiquitin ligase activity. Our findings define the essential role of RNF220 in spermatogenesis and provide novel molecular insights into the pathogenesis of male infertility.
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BibTeX
@article{cha2026rnf220,
title = {{RNF220 safeguards meiotic synapsis and male fertility by antagonizing SYCE1 ubiquitination.}},
author = {Jingmei Cha and Huijuan Lin and Yingqian Xia and Jianlin Xu and Pengcheng Ma and Shuhua Zhao and Bingyu Mao},
journal = {Cell death \& disease},
year = {2026},
month = jul,
doi = {10.1038/s41419-026-09128-8},
url = {https://europepmc.org/article/MED/42901904},
note = {CC BY},
}
RIS
TY - JOUR
TI - RNF220 safeguards meiotic synapsis and male fertility by antagonizing SYCE1 ubiquitination.
AU - Jingmei Cha
AU - Huijuan Lin
AU - Yingqian Xia
AU - Jianlin Xu
AU - Pengcheng Ma
AU - Shuhua Zhao
AU - Bingyu Mao
PY - 2026
DA - 2026/07/01
JO - Cell death & disease
DO - 10.1038/s41419-026-09128-8
UR - https://europepmc.org/article/MED/42901904
AB - A homozygous mutation in RNF220, encoding a RING-type E3 ubiquitin ligase, is associated with male infertility featuring small-headed sperm, but the precise roles and mechanisms of RNF220 in spermatogenesis remain elusive. Here, we explored the function of RNF220 in spermatogenesis using a Stra8-Cre-mediated germ cell-specific conditional knockout mouse model. RNF220 was highly expressed in mouse spermatocytes, and its germ cell-specific deletion caused male subfertility, accompanied by testicular atrophy, oligozoospermia, and abnormal sperm morphology. Spermatocyte nuclear spreading assay revealed severe defects in homologous chromosome synapsis and DNA damage repair, as well as elevated apoptosis in pachytene spermatocytes. Mechanistically, SYCE1, a core component of the synaptonemal complex central element essential for synapsis, was identified as a testicular target of RNF220. Notably, RNF220 stabilized SYCE1 by antagonizing its ubiquitination mediated by other ubiquitin ligases. RNF220 deficiency led to reduced SYCE1 protein level and marked increase in its K48-linked polyubiquitination. Furthermore, RNF220-mediated SYCE1 stabilization was independent of its intrinsic ubiquitin ligase activity. Our findings define the essential role of RNF220 in spermatogenesis and provide novel molecular insights into the pathogenesis of male infertility.
SN - 2041-4889
ER -