Eif4enif1, also known as eukaryotic translation initiation factor 4E nuclear import factor 1, encodes an eukaryotic translation initiation factor 4E transporter (4E-T) protein. It plays a crucial role in inhibiting mRNA translation and regulating mRNA destabilization [3]. It is associated with pathways related to ovarian function and development [2]. Genetic models, especially mouse models, are valuable for studying its functions.

In mouse models, Eif4enif1 haploinsufficiency causes subfertility, impairs oocyte maturation and partially arrests early embryonic development. Dual-omic sequencing shows it significantly alters both the transcriptome and translatome in mouse oocytes, leading to oocyte mitochondrial hyperfusion and mitochondria-associated ribonucleoprotein domain distribution alteration [1]. In human studies, various Eif4enif1 variants have been identified in patients with non-syndromic premature ovarian insufficiency (POI). These variants exhibit reduced mRNA and protein expression levels and impaired translation regulation abilities, potentially causing POI via impaired translation repression [3,4].

In conclusion, Eif4enif1 is essential for regulating mRNA translation and stability, with a significant impact on ovarian function. Mouse models with Eif4enif1 haploinsufficiency have been instrumental in revealing its role in female infertility, providing new insights into the molecular mechanisms underlying clinical fertility failure and potential therapeutic targets for infertility treatment [1].

References:

1. Ding, Yuxi, He, Zequn, Sha, Yanwei, Kee, Kehkooi, Li, Lin. 2023. Eif4enif1 haploinsufficiency disrupts oocyte mitochondrial dynamics and leads to subfertility. In Development (Cambridge, England), 150, . doi:10.1242/dev.202151. https://pubmed.ncbi.nlm.nih.gov/38088064/

2. França, Monica Malheiros, Mendonca, Berenice Bilharinho. 2021. Genetics of ovarian insufficiency and defects of folliculogenesis. In Best practice & research. Clinical endocrinology & metabolism, 36, 101594. doi:10.1016/j.beem.2021.101594. https://pubmed.ncbi.nlm.nih.gov/34794894/

3. Shang, Lingyue, Ren, Shuting, Yang, Xi, Zhang, Xiaojin, Wu, Yanhua. 2022. EIF4ENIF1 variants in two patients with non-syndromic premature ovarian insufficiency. In European journal of medical genetics, 65, 104597. doi:10.1016/j.ejmg.2022.104597. https://pubmed.ncbi.nlm.nih.gov/36030004/

4. Ding, Yuxi, Chen, Shuya, Jin, Jing, Xin, Mingwei, Li, Lin. 2024. POI-associated EIF4ENIF1 mutations exhibit impaired translation regulation abilities. In Gene, 917, 148456. doi:10.1016/j.gene.2024.148456. https://pubmed.ncbi.nlm.nih.gov/38604507/