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<p>Genomic instability is the main cause of abnormal embryo development and abortion. NLRP7 dysfunctions affect embryonic development and lead to Hydatidiform Moles, but the underlying mechanisms remain largely elusive. Here, we show that <i>NLRP7</i> knockout affects the genetic stability, resulting in increased DNA damage in both human embryonic stem cells and blastoids, making embryonic cells in blastoids more susceptible to apoptosis. Mechanistically, NLRP7 can interact with factors related to alternative splicing and DNA damage response, including DDX39B, PRPF8, THRAP3 and PARP1. Moreover, <i>NLRP7</i> dysfunction leads to abnormal alternative splicing of genes involved in homologous recombination in human embryonic stem cells, Such as <i>Brca1</i> and <i>Rad51</i>. These results indicate that NLRP7-mediated Alternative splicing is potentially required for the maintenance of genome integrity during early human embryogenesis. Together, this study uncovers that NLRP7 plays an essential role in the maintenance of genetic stability during early human embryonic development by regulating alternative splicing of homologous recombination-related genes.</p>

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NLRP7 maintains the genomic stability during early human embryogenesis via mediating alternative splicing

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月26日

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  • Zhongliang Chen,
  • Liangxia Jiang,
  • Min Su,
  • Qibing Zeng,
  • Peng Luo,
  • Liangzhao Chu

摘要

Genomic instability is the main cause of abnormal embryo development and abortion. NLRP7 dysfunctions affect embryonic development and lead to Hydatidiform Moles, but the underlying mechanisms remain largely elusive. Here, we show that NLRP7 knockout affects the genetic stability, resulting in increased DNA damage in both human embryonic stem cells and blastoids, making embryonic cells in blastoids more susceptible to apoptosis. Mechanistically, NLRP7 can interact with factors related to alternative splicing and DNA damage response, including DDX39B, PRPF8, THRAP3 and PARP1. Moreover, NLRP7 dysfunction leads to abnormal alternative splicing of genes involved in homologous recombination in human embryonic stem cells, Such as Brca1 and Rad51. These results indicate that NLRP7-mediated Alternative splicing is potentially required for the maintenance of genome integrity during early human embryogenesis. Together, this study uncovers that NLRP7 plays an essential role in the maintenance of genetic stability during early human embryonic development by regulating alternative splicing of homologous recombination-related genes.