Faculty Collaboration Database

RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site. Cell Rep 2021 Nov 02;37(5):109934

Date

11/04/2021

Pubmed ID

34731628

Pubmed Central ID

PMC8675433

DOI

10.1016/j.celrep.2021.109934

Scopus ID

2-s2.0-85118477211 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

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.

Author List

George J, Li Y, Kadamberi IP, Parashar D, Tsaih SW, Gupta P, Geethadevi A, Chen C, Ghosh C, Sun Y, Mittal S, Ramchandran R, Rui H, Lopez-Berestein G, Rodriguez-Aguayo C, Leone G, Rader JS, Sood AK, Dey M, Pradeep S, Chaluvally-Raghavan P

Authors

Pradeep Chaluvally-Raghavan PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Anjali Geethadevi PHD Research Scientist I in the Obstetrics and Gynecology department at Medical College of Wisconsin
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of Wisconsin
Deepak Parashar PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
Yunguang Sun MD, PhD Assistant Professor in the Pathology department at Medical College of Wisconsin
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

3' Untranslated Regions
AU Rich Elements
Animals
Cell Line, Tumor
Cell Proliferation
Cell Survival
Eukaryotic Initiation Factor-4F
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Nude
Ovarian Neoplasms
Peptide Chain Initiation, Translational
Proto-Oncogene Proteins c-myc
RNA Stability
RNA, Messenger
RNA-Binding Proteins
Signal Transduction
Tumor Burden