Bi-allelic Pathogenic Variants in PABPC1L Cause Oocyte Maturation Arrest and Female Infertility

ABSTRACT: Oocyte maturation arrest is one of the important causes of female infertility, but the genetic factors remain largely unknown. PABPC1L, a predominant poly(A)-binding protein in Xenopus, mouse, and human oocytes and early embryos prior to zygotic genome activation, plays a key role in translational activation of maternal mRNAs. Here, we identified compound heterozygous and homozygous variants in PABPC1L that are responsible for female infertility mainly characterized by oocyte maturation arrest. In vitro studies demonstrated that these variants resulted in truncated proteins, reduced protein abundance, altered cytoplasmic localization, and reduced mRNA translational activation by affecting the binding of PABPC1L to mRNA. In vivo, three strains of Pabpc1l knock-in (KI) female mice were infer

SUBMITTER: Dr. Lei Wang 

PROVIDER: S-SCDT-10_15252-EMMM_202217177 | biostudies-other |

REPOSITORIES: biostudies-other