RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site

Fragile X-related protein-1 (FXR1) gene is highly amplified in patients with ovarian cancer, and this amplification is associated with increased expression of both FXR1 mRNA and protein. FXR1 expression directly associates with the survival and proliferation of cancer cells. Surface sensing of translation (SUnSET) assay demonstrates that FXR1 enhances the overall translation in cancer cells. Reverse-phase protein array (RPPA) reveals that cMYC is the key target of FXR1. Mechanistically, FXR1 binds to the AU-rich elements (ARE) present within the 3' untranslated region (3'UTR) of cMYC and stabilizes its expression. In addition, the RGG domain in FXR1 interacts with eIF4A1 and eIF4E proteins. These two interactions of FXR1 result in the circularization of cMYC mRNA and facilitate the recruitment of eukaryotic translation initiation factors to the translation start site. In brief, we uncover amechanism by which FXR1 promotes cMYC levels in cancer cells.

Automated summary

The FXR1 gene is highly amplified in patients with ovarian cancer, leading to increased expression of FXR1 mRNA and protein. FXR1 enhances overall translation in cancer cells and stabilizes cMYC expression by binding to AU-rich elements within cMYC's 3' untranslated region. Additionally, FXR1's interactions with eIF4A1 and eIF4E proteins facilitate the recruitment of translation initiation factors to promote cMYC levels in cancer cells.