The protein encoded by this gene is a nucleocytoplasmic shuttle protein for the translation initiation factor eIF4E. This shuttle protein interacts with the importin alpha-beta complex to mediate nuclear import of eIF4E. It is predominantly cytoplasmic;its own nuclear import is regulated by a nuclear localization signal and nuclear export signals.
Apoptosis, Translation factor
Clast4, the murine homologue of human eIF4E-Transporter, is highly expressed in developing oocytes and post-translationally modified at meiotic maturation Villaescusa JC, et al .
In metazoans, translational regulation of a set of maternal mRNAs directs oocyte maturation and early embryogenesis. These transcripts are often kept dormant until their products are spatially and temporally required in development. The interaction between general translation factors (i.e. eIF4E) and their specific interactors influences translation initiation. A search of the protein database for a mouse homologue of the Drosophila Cup protein, a translational repressor during female germ-line development, identified the product of the Clast4 gene. In this report, we show that Clast4 mRNA and protein are highly expressed within the cytoplasm of growing oocytes. The Clast4 protein is stable during this developmental window and post-translationally modified by phosphorylation upon oocyte meiotic maturation. Additionally, we show that Clast4 and eIF4E directly interact by means of a canonical and functional eIF4E-binding motif. Our results suggest that Clast4, similar to Drosophila Cup, may act at the translational level during murine female germ-line development.
Expression regulated by
POF (premature ovarian failure)
Mutation name: None
type: naturally occurring fertility: subfertile Comment: Mutations in eIF4ENIF1 Are Associated With Primary Ovarian Insufficiency. Kasippillai T 2013 et al.
Context:Primary ovarian insufficiency (POI), or premature ovarian failure, results from ovarian follicle depletion with a consequent elevation of FSH levels before age 40 years. We identified a family in which 9 women in 3 consecutive generations developed menopause at approximately age 30 years. We hypothesized a genetic cause with a dominant mode of inheritance.Design:This was a family-based genetic study and a replicate group of women with POI.Setting:The study was conducted at an academic medical center.Patients:Seven affected women and an obligate carrier and 7 unaffected family members were genotyped. The genes of interest were also sequenced in 38 unrelated women with POI.Intervention:The DNA from 7 family members was subjected to whole-exome sequencing. The genotypes of interest were confirmed and genotypes of additional family members and unrelated women with POI were determined using Sanger sequencing.Main Outcome Measure:A high-impact, deleterious variant that segregated appropriately with POI in the family was measured.Results:A heterozygous stop codon (Ser429X) was identified in the eukaryotic translation initiation factor 4E nuclear import factor 1 (eIF4ENIF1) in the proband and all affected women but not in the unaffected family members. The chance that such a high-impact, deleterious variant would segregate appropriately among the affected and unaffected relatives by chance is very low (P < .05). There were no additional mutations identified in eIF4ENIF1 or eIF4E in 38 unrelated women with POI.Conclusion:Data demonstrate a new gene associated with dominantly inherited POI. These results highlight the importance of translation initiation factors and their regulators in ovarian function.