CCDC174 deficiency impaired human fertility by affecting the alternative splicing of maternal mRNAs

ABSTRACT: Precise regulation of alternative splicing (AS) of maternal mRNAs is crucial for maintaining mRNA homeostasis and for acquiring oocyte competence. However, the regulatory factors and mechanisms of AS regulating oocyte competence and human fertility remain largely unknown. Here, we identified biallelic variants in CCDC174 that cause human oocyte competence defects and female infertility. Oocyte-specific knockout of Ccdc174 resulted in oocyte maturation arrest and female infertility in mice, and transcriptomic and proteomic analyses indicated that deletion of Ccdc174 disrupted mRNA and protein homeostasis as well as AS in oocytes. Importantly, we found that CCDC174 interacted with the splicing machinery-related PRP19/CDC5L complex, and loss of CCDC174 led to aberrant activation of the expres

SUBMITTER: Weijie Wang 

PROVIDER: S-SCDT-10_1038-S44321-026-00448-Y | biostudies-other |

REPOSITORIES: biostudies-other