PARP7-mediated mono-ADP-ribosylation stabilizes MYH9 to ensure actin cap integrity and chromosome segregation in mouse oocytes.
Source: PubMed, NCBI / U.S. National Library of Medicine
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. 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. Metabolomic profiling was performed to assess NADdynamics 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. 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. 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 reproductive
Abstract
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. 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. Metabolomic profiling was performed to assess NADdynamics 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. 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. 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 reproductive decline.