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

Guangyi Cao1, Sipei Liu2, Yanbo Liu2

  • 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing 210008, China; Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Jiangsu Human Reproductive Function Remodeling Engineering Research Center, Nanjing 210008, China; Nanjing Clinical Medical Center for Reproductive Medicine, Nanjing, Jiangsu, 210008, China.

Abstract

Insights

Poly (ADP-ribose) polymerase 7 (PARP7) stabilizes MYH9, maintaining the actin cap for proper chromosome segregation during mouse oocyte meiosis. This is crucial for preventing aneuploidy and understanding reproductive aging.

Area of Science:

  • Cell Biology
  • Reproductive Biology
  • Biochemistry

Background:

  • Oocyte meiotic maturation involves asymmetric cell division, spindle migration, and actin cap formation.
  • Upstream regulators of these coordinated events in oocytes are not fully understood.

Purpose of the Study:

  • Investigate the role of PARP7, a mono-ADP-ribosyltransferase, in mouse oocyte meiosis.
  • Determine its function in regulating actin dynamics and chromosomal stability.

Main Methods:

  • NAD+ dynamics assessed via metabolomic profiling.
  • PARP7 expression and localization analyzed through genetic knockdown and inhibition.
  • Multi-omics analyses identified PARP7 targets and MARylation sites; protein stability evaluated.

Main Results:

  • PARP7 is the most abundant PARP in oocytes, localizing to the actin cap.
  • PARP7 inhibition caused meiotic failure, cytokinesis issues, and aneuploidy due to impaired actin cap formation.
  • MYH9 identified as a PARP7 target; its MARylation is critical for stability, preventing rapid degradation.

Conclusions:

  • PARP7-mediated MARylation stabilizes MYH9, ensuring actin cap integrity and chromosomal segregation in oocytes.
  • Findings offer insights into oocyte aneuploidy and age-related reproductive decline.

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