Abstract
Recent whole-exome sequencing (WES) studies demonstrated that TRAIP is associated with primordial dwarfism. Although TRAIP was partially studied in mitosis, its function in oocyte meiosis remained unknown. In this study, we investigated the roles of TRAIP during mouse oocyte meiosis. TRAIP was stably expressed during oocytes meiosis and co-localized with CREST at the centromere region. Knockdown of TRAIP led to DNA damage, as revealed by the appearance of γH2AX. Although oocytes meiotic maturation was not affected, the proportions of misaligned chromosomes and aneuploidy were elevated after TRAIP knockdown, suggesting TRAIP is required for stable kinetochore–microtubule (K-MT) attachment. TRAIP knockdown decreased the accumulation of Mad2 on centromeres, potentially explaining why oocyte maturation was not affected following formation of DNA lesions. Securin, a protein which was prevent from precocious degradation by Mad2, was down-regulated after TRAIP knockdown. Inhibition of TRAIP by microinjection of antibody into pro-metaphase I (pro-MI) stage oocytes resulted in precocious first polar body (PB1) extrusion, and live-cell imaging clearly revealed misaligned chromosomes after TRAIP knockdown. Taken together, these data indicate that TRAIP plays important roles in oocyte meiosis regulation.
Highlights
Recent whole-exome sequencing (WES) studies demonstrated that TRAIP is associated with primordial dwarfism
The tumor necrosis factor (TNF) receptor-associated factor (TRAF)-interacting protein (TRAIP) is a Real Interesting New Gene (RING)-type E3 ubiquitin ligase involved in tumor necrosis factor-α (TNF-α)-mediated NF-κB activation[17,18]
We found that TRAIP was stably expressed and localized to the centromeres during mouse oocyte meiosis
Summary
Recent whole-exome sequencing (WES) studies demonstrated that TRAIP is associated with primordial dwarfism. Inhibition of TRAIP by microinjection of antibody into pro-metaphase I (pro-MI) stage oocytes resulted in precocious first polar body (PB1) extrusion, and live-cell imaging clearly revealed misaligned chromosomes after TRAIP knockdown. Taken together, these data indicate that TRAIP plays important roles in oocyte meiosis regulation. The tumor necrosis factor (TNF) receptor-associated factor (TRAF)-interacting protein (TRAIP) is a RING-type E3 ubiquitin ligase involved in tumor necrosis factor-α (TNF-α)-mediated NF-κB activation[17,18] In both human and mouse, the protein is composed of 469 amino acids and encoded by 15 exons. TRAIP is identified as a primordial dwarfism associated gene and is involved in DDR during genome replication[25]
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