PARP7-mediated mono-ADP-ribosylation stabilizes MYH9 to ensure actin cap integrity and chromosome segregation in mouse oocytes

作者：Cao Guang-yi, Sipei Liu, Yanbo Liu, Anqi Chen, Qian Xu, Lina Yu, Aolei Guo, Yan Mao, Ganggui Lou, Chaojun Li, Luhong Wen, Guijun Yan, Haixiang Sun · 发表于：Journal of Advanced Research · 年份：2026 · DOI：10.1016/j.jare.2026.08.012 · 研究领域：PARP inhibition in cancer therapy、Reproductive Biology and Fertility、Cellular Mechanics and Interactions

INTRODUCTION: Oocyte meiotic maturation requires highly asymmetric cell division, governed by spindle migration and actin cap formation. However, the upstream mechanisms that regulate the precise coordination of these events remain unclear. OBJECTIVES: This study aimed to elucidate the role of PARP7, a mono-ADP-ribosyltransferase, in regulating actin cytoskeletal dynamics and chromosomal stability during mouse oocyte meiosis. METHODS: dynamics during meiosis. PARP7 expression and localisation were analysed using genetic knockdown and pharmacological inhibition approaches. Multi-omics analyses were performed to identify PARP7 targets and map MARylation sites within the motor domain. Protein stability was evaluated following PARP7 suppression and site-directed mutagenesis. RESULTS: PARP7 was identified as the most abundant PARP family member in oocytes and localised to the actin cap during anaphase I. PARP7 inhibition disrupted meiotic progression, resulting in cytokinesis failure, aberrant polar body extrusion, and increased aneuploidy. These defects were attributed to impaired actin cap formation. MYH9 was identified as a PARP7 target, and MARylation was found to be critical for its stability; loss of this modification accelerated MYH9 degradation. CONCLUSION: PARP7-mediated MARylation stabilises MYH9 to maintain actin cap integrity and chromosomal segregation in mouse oocytes. These findings provide novel insights into the aetiology of oocyte aneuploidy and age-related repro...