Cell Reports (Nov 2021)
RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site
- Jasmine George,
- Yongsheng Li,
- Ishaque P. Kadamberi,
- Deepak Parashar,
- Shirng-Wern Tsaih,
- Prachi Gupta,
- Anjali Geethadevi,
- Changliang Chen,
- Chandrima Ghosh,
- Yunguang Sun,
- Sonam Mittal,
- Ramani Ramchandran,
- Hallgeir Rui,
- Gabriel Lopez-Berestein,
- Cristian Rodriguez-Aguayo,
- Gustavo Leone,
- Janet S. Rader,
- Anil K. Sood,
- Madhusudan Dey,
- Sunila Pradeep,
- Pradeep Chaluvally-Raghavan
Affiliations
- Jasmine George
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Yongsheng Li
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Hainan Medical University, Haikou 571199, China
- Ishaque P. Kadamberi
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Deepak Parashar
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Shirng-Wern Tsaih
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Prachi Gupta
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Anjali Geethadevi
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Changliang Chen
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Chandrima Ghosh
- Department of Biological Sciences, University of Wisconsin, Milwaukee, WI 53211, USA
- Yunguang Sun
- Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Sonam Mittal
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Ramani Ramchandran
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Hallgeir Rui
- Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Gabriel Lopez-Berestein
- Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
- Cristian Rodriguez-Aguayo
- Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
- Gustavo Leone
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Medical College of Wisconsin Cancer Center, Milwaukee, WI 53226, USA
- Janet S. Rader
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Anil K. Sood
- Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA; Department of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA
- Madhusudan Dey
- Department of Biological Sciences, University of Wisconsin, Milwaukee, WI 53211, USA
- Sunila Pradeep
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Medical College of Wisconsin Cancer Center, Milwaukee, WI 53226, USA
- Pradeep Chaluvally-Raghavan
- Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Center of Systems Molecular Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Medical College of Wisconsin Cancer Center, Milwaukee, WI 53226, USA; Corresponding author
- Journal volume & issue
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Vol. 37,
no. 5
p. 109934
Abstract
Summary: 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 a mechanism by which FXR1 promotes cMYC levels in cancer cells.
