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

ABSTRACT: 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 Altern

SUBMITTER: Chen Z 

PROVIDER: S-EPMC11770114 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature